CN110585358B - Application of sorghum bran total flavonoids in preventing and treating gout diseases - Google Patents
Application of sorghum bran total flavonoids in preventing and treating gout diseases Download PDFInfo
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- CN110585358B CN110585358B CN201910971304.5A CN201910971304A CN110585358B CN 110585358 B CN110585358 B CN 110585358B CN 201910971304 A CN201910971304 A CN 201910971304A CN 110585358 B CN110585358 B CN 110585358B
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- sorghum bran
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- uric acid
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K2236/30—Extraction of the material
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- A—HUMAN NECESSITIES
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- A61K2236/55—Liquid-liquid separation; Phase separation
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Mycology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- General Chemical & Material Sciences (AREA)
- Nutrition Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
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- Medicines Containing Plant Substances (AREA)
Abstract
The invention relates to application of Sorghum (Sorghum bicolor (L.) Moench) bran total flavone in inhibiting uric acid increase and preventing and treating gout. The sorghum bran total flavone belongs to a pure natural product, is a byproduct in a sorghum rice processing process, and is proved by research to contain rich flavonoid substances, and has the effects of inhibiting uric acid increase and preventing and treating gout diseases.
Description
Technical Field
The invention relates to a preparation method for extracting total flavonoids from sorghum bran, which is proved to have new medical application by pharmacological experiments. In particular to sorghum bran total flavonoids which have the effect of inhibiting the increase of uric acid and have the effect of preventing and treating gout diseases. Belongs to the field of traditional Chinese medicine.
Background
Gout is an inflammatory arthritis characterized by a disabling acute episode of pain. It is a symptom caused by hyperuricemia, which is the main cause of gout, and the deposition of urate crystals around joints. Studies have shown that hyperuricemia is associated with altered expression and function of the urate transporter. Chronic increases in serum uric acid levels or hyperuricemia are the major pathological condition for gout development.
Epidemiological survey data show that in recent years, the incidence rate of hyperuricemia in Chinese population is also in a straight-line rising and young trend, and the incidence rate of hyperuricemia in China is increased by about 10 times from 1996-2006, and the hyperuricemia becomes the clinical 'fourth highest' after hypertension, hyperlipidemia and hyperglycemia. According to conservative estimation, the number of hyperuricemia patients in China currently reaches 1.2 hundred million, and accounts for about 9.0 percent of the total number of the people. Hyperuricemia is not regarded by people because of no obvious clinical symptoms. However, in fact, one of the main effects of long-term hyperuricemia on human body is gout caused by deposition of urate crystals on joints and kidneys, hyperuricemia is an important biochemical basis for gout, and about 5% -12% of patients with hyperuricemia develop gout. Gout not only can invade bones and joints, but also easily affects the kidney and cardiovascular system. More importantly, a great deal of epidemiological studies at home and abroad show that hyperuricemia is closely related to a plurality of components of metabolic syndrome, such as obesity, hypertension, dyslipidemia, hyperglycemia, coronary heart disease, insulin resistance and the like, becomes a part of the metabolic syndrome, and is in positive correlation with diseases such as obesity, hyperlipidemia, hypertension, diabetes, atherosclerosis and the like. Has synergistic effect with hypertension, insulin resistance, obesity, hyperlipidemia, and glucose tolerance abnormality, and can be used for treating arteriosclerosis and cardiovascular and cerebrovascular diseases. Therefore, hyperuricemia has become an important disease threatening human health.
Hyperuricemia has long been almost completely dependent on allopurinol, but a clinically significant proportion of patients with hyperuricemia are unable to achieve the recommended control target for serum uric acid concentration by treatment with allopurinol. In addition, although allopurinol is safe, it has an increased incidence and severity of side effects in patients with impaired renal function. Newer uric acid lowering drugs such as febuxostat and pegroglucinol have certain side effects in clinical application, such as elevated liver enzyme levels, rashes, diarrhea, headache, nausea, contusion/ecchymosis, nasopharyngitis, constipation, vomiting, and the like. Therefore, the search for a new safe and effective functional component for reducing uric acid has important practical significance and application value.
The sorghum bran accounts for about 12% of the mass of the sorghum grains, contains a large amount of procyanidine, anthocyanin, tannin, phenols, sterol, flavone and the like, has high oxidation resistance, and therefore, the sorghum bran also has the effects of resisting and preventing cancers. The sorghum bran has high nutritional value, contains a certain amount of starch and a certain amount of protein, and in addition, trace elements such as iron, calcium and scales are also the most important elements in the sorghum bran, besides the trace elements, sugars, vitamins and fat are also important elements in the sorghum bran, and at ordinary times, the sorghum bran can absorb various nutritional ingredients when people eat the sorghum bran, so that the sorghum bran has great benefits for promoting body metabolism. The sorghum bran has high medicinal value, sweet and astringent taste and warm nature, can harmonize the stomach, invigorate the spleen and check diarrhea, can treat food retention and dyspepsia of human beings by eating at ordinary times, and has good conditioning effect on various adverse symptoms such as damp heat, diarrhea, dysuria and the like of human beings. Meanwhile, dietary fiber contained in the sorghum bran can regulate gastrointestinal functions and promote gastrointestinal peristalsis.
The invention can further expand the development and utilization of the sorghum bran and has good social benefit and considerable economic benefit.
Before the completion of the invention, the preparation method of the sorghum bran total flavone and the report of inhibiting the increase of uric acid are not available.
Disclosure of Invention
The invention aims to provide a new application of sorghum bran total flavonoids, in particular to an application of the sorghum bran total flavonoids in uric acid control, and more particularly an application of the sorghum bran total flavonoids in medicines and health care products for preventing and treating hyperuricemia and gout.
The invention aims to provide Sorghum bran total flavonoids which are obtained by extracting and purifying bran of Sorghum bicolor (L.) Moench of Gramineae, wherein the content of the total flavonoids is more than 80%.
The invention has the outstanding contribution that: the sorghum bran composition is obtained by enriching total flavonoids from the novel medical and edible dual-purpose resource sorghum bran, and has the effect of inhibiting uric acid rise. The invention provides a new medicine resource and a new medicine application, which are the most outstanding contribution and the most remarkable innovation of the invention.
According to the invention, water is firstly adopted for soaking to remove components such as saponin, water-soluble polysaccharide and elements, then ethanol containing calcium oxide is used for extraction, the extract is not concentrated, and is directly adsorbed and purified by a macroporous resin column, so that the problem that the ethanol extract has a large amount of precipitates after concentration and is not beneficial to adsorption and purification on the resin column is solved. The invention is characterized in that the invention is firstly soaked in water to remove a large amount of water-soluble impurities, then is extracted by ethanol containing calcium oxide to remove some phenolic acid and tannin components, and the fat-soluble impurity components are removed from the extract through a resin column, which is also one of the innovation points of the invention.
Another object of the present invention is to provide a method for preparing total flavonoids extracted from sorghum bran, which is characterized in that: extracting sorghum bran raw material with 35-50 deg.C warm water for 1-3 times, each time for 8-12 hr, filtering, collecting the extracted sorghum bran, extracting with 4-8 times of 60-90% ethanol containing 1-3% calcium oxide for 1-3 times, filtering, collecting ethanol extractive solution, decolorizing with 1-2% ethanol volume of activated carbon, and filtering to obtain ethanol extractive solution; taking the ethanol extract, passing through D101 macroporous resin adsorption resin treated by 60-90% ethanol in advance, eluting by 1-3 times of column volume by using 60-90% ethanol, collecting effluent and eluate, recovering ethanol, filtering, washing filter cakes with water, and drying to obtain the sorghum bran total flavonoids.
Further preferably: extracting sorghum bran raw material with 50 deg.C warm water for 3 times, each for 12 hr, filtering, collecting the extracted sorghum bran, extracting with 7 times of 80% ethanol containing 2% calcium oxide for 3 times, filtering, collecting ethanol extractive solution, decolorizing with 2% ethanol volume of activated carbon, and filtering to obtain ethanol extractive solution; taking the ethanol extract, passing through D101 macroporous resin adsorption resin treated by 80% ethanol in advance, eluting by 1 time of column volume by 80% ethanol, collecting effluent and eluate, recovering ethanol, filtering, washing filter cake with water, and drying to obtain sorghum bran total flavone.
The invention discloses that the sorghum bran total flavonoids have the effect of inhibiting the increase of uric acid for the first time, so that the sorghum bran total flavonoids are prepared into a medicament independently or in combination with other active components or auxiliary materials, and the medicament has the effect of inhibiting the increase of uric acid and belongs to the protection scope of the invention. The composition of the invention has the function of inhibiting the increase of uric acid when being prepared into any dosage form, and is within the protection scope of the invention.
In order to realize the technical scheme, the content of the sorghum bran total flavonoids is determined by the following method:
preparation of reference solution rutin reference 10mg is precisely weighed, placed in a 100ml measuring flask, dissolved by methanol and diluted to scale, shaken up, 5ml is precisely weighed, placed in a 10ml measuring flask, diluted to scale by methanol and shaken up, thus obtaining the rutin reference.
Preparing a test solution, precisely weighing 50mg sorghum bran total flavone powder, adding an appropriate amount of methanol into a 50ml volumetric flask, carrying out ultrasonic treatment for 20min, taking out, standing at room temperature, adding methanol to a constant volume to a scale, shaking up, taking out from a 2ml volumetric flask to a 25ml volumetric flask, adding methanol to a constant volume to a scale, and thus obtaining the sorghum bran total flavone powder.
The determination method comprises respectively taking reference solution, test solution, and accompanying blank. The absorbance was measured at a wavelength of 340nm by spectrophotometry (appendix V B of 2010 edition, Chinese pharmacopoeia).
The sorghum bran total flavonoids (called total flavonoids for short) have the effects of preventing and treating hyperuricemia, and the pharmacological effects are proved by the following pharmacodynamic test examples.
Experiment raw materials: the sorghum bran total flavonoids used in the pharmacodynamics are provided by the inventor. Prepared according to example 1. The allopurinol used in the pharmacodynamic test isGuangxi Pidi pharmaceutical Co., LtdProduction (batch number: 20180301).
1. Acute toxicity Experimental study
20 mice, 18-20 g, are selected, and the male and female are half each. The maximum dose concentration (0.5g/ml) and the maximum dose volume (0.4ml/10g body weight) which can be tolerated by animals are intragastrically administered for 1 time a day, and the non-toxic reaction and the death of the animals are continuously observed within 7 days. The measured results are: none of the animals died within 7 days of the mice, and no significant acute toxic response was observed at this dose. The maximum dosage of the mouse is 10g of medicinal powder/kg of body weight/d. The administration dose is about 100 times the daily dose of the clinical drug calculated on the basis of 70kg body weight.
2. Influence of sorghum bran total flavonoids on mouse hyperuricemia (oteracil potassium salt method)
60 Kunming mice are taken. The male and female are half. The test pieces were randomly divided into 6 groups (normal control group, model group, high, medium and low total flavone dose group, allopurinol group). The composition is administered 1 time per day for 5 days. After 1 hour of the last administration, the animals of the other groups except the blank group were injected with 300mg/kg of Potassium Oxonate intraperitoneally to cause hyperuricemia in mice. After 1h of injection, each group of animals takes eyeballs and blood, centrifuges for 5min at 2500r/min, takes serum to measure blood uric acid value, and performs difference comparison among groups. The results are shown in Table 1.
Table 1 effect of sorghum bran total flavonoids on hyperuricemia in mice (n ═ 10, X ± S)
Note: Δ <0.01 in comparison to blank set, P <0.01 in comparison to model set
The sorghum bran total flavone has good inhibition effect on hyperuricemia model blood uric acid caused by mice (oteracil potassium salt) by each dosage group.
3. Influence of sorghum bran total flavonoids on mouse blood uric acid (xanthine method)
60 male mice were randomly divided into 6 groups (normal control group, model group, high, medium, and low total flavone dose group, allopurinol group) of 10 mice each. The stomach was perfused with 0.1mL · l0g daily. After 6 days, except for the normal control group, 5 groups of mice were each intraperitoneally injected with 0.1 mL. multidot.l.multidot.0 0g of 10% xanthine, and blood was taken after 30min to measure the blood uric acid level.
Table 2 effect of sorghum bran total flavonoids on mouse serum uric acid (n ═ 10, X ± S)
Comparison of Δ to blank group: p <0.01, compared to model group P < 0.01.
The blood uric acid content of the model group is obviously higher than that of the normal control group, the difference has obvious significance (P <0.01), and the blood uric acid content difference of the medicine group and the model group is very obvious and is lower than that of the model group (P <0.0 l). Further shows that the mechanism of reducing the content of the blood uric acid by the sorghum bran total flavonoids is the reduction of the generation of uric acid like allopurinol. Reduces the damage to the tissues, thereby effectively controlling the gout attack.
From the toxicity and pharmacodynamic experiments, the sorghum bran total flavonoids have the effect of inhibiting the generation of uric acid, so that the gout can be treated and prevented, side effects are avoided after long-term administration, and the sorghum bran total flavonoids can be prepared into oral preparations and are convenient to take.
Detailed Description
The present invention is realized (demonstrated) by the following examples, but the technical solution of the present invention is not limited thereto.
EXAMPLE 1 preparation of sorghum bran Total Flavonoids
Extracting 50kg of sorghum bran raw material with warm water at 50 ℃ for 3 times, each time for 12 hours, filtering, collecting the extracted sorghum bran, extracting with 7 times of 80% ethanol containing 2% calcium oxide for 3 times, filtering, collecting ethanol extract, decolorizing with activated carbon with 2% ethanol volume, and filtering to obtain ethanol extract; taking the ethanol extract, passing through D101 macroporous resin adsorption resin treated by 80% ethanol in advance, eluting by 1 time of column volume by 80% ethanol, collecting effluent and eluate, recovering ethanol, filtering, washing filter cake with water, and drying to obtain 1254.8g of sorghum bran total flavonoids with total flavone content of 86.7%.
Example 2 (Capsule)
Prescription: sorghum bran Total Flavonoids: 200g
Starch: 40g of
Sodium carboxymethyl starch: 10g
Proper amount of 3% hydroxy-methyl cellulose aqueous solution
Mixing sorghum bran total flavone raw material, starch and sodium carboxymethyl starch uniformly, granulating with 3% hydroxypropyl methyl cellulose water solution, drying, grading, and making into No. 0 capsule, and making into 1000 granules. Each grain contains sorghum bran total flavone 200 mg. 2 granules at a time. It is administered 2 times daily.
Example 3 (tablet)
Prescription: sorghum bran Total Flavonoids: 200g
Lactose: 40g of
Sodium carboxymethyl starch: 7.5g
Proper amount of 3% hydroxypropyl methylcellulose aqueous solution
Talc powder: 2.5g
Mixing sorghum bran total flavone raw material, lactose and sodium carboxymethyl starch uniformly, granulating with 3% hydroxypropyl methyl cellulose water solution, drying, grading, adding pulvis Talci, mixing, and tabletting to obtain 1000 tablets. Each tablet contains sorghum bran total flavone 200 mg. 2 tablets at a time. It is administered 3 times daily.
Example 4 (granules)
Prescription: sorghum bran Total Flavonoids: 200g
Sugar powder: 300g
Mixing sorghum bran total flavone raw material and sugar powder uniformly, granulating with appropriate amount of ethanol, drying, grading, packaging, and making into 500 bags. 1 bag at a time. It is administered 2 times daily.
Example 5 (drop pill)
Prescription: sorghum bran Total Flavonoids: 20g of
Polyethylene glycol 6000: 25g of
Polyethylene glycol 4000: 15g of
Weighing 25g of polyethylene glycol 6000 and 10g of polyethylene glycol 4000, melting in a water bath, adding 15g of sorghum bran total flavone raw material, uniformly stirring, pouring into a heat preservation pipe, adjusting a constant temperature device, dripping the liquid medicine into cooled liquid paraffin (12-14 ℃) at 80-90 ℃, pouring pills into filter paper, and sucking off paraffin oil to prepare 1000 pills. 20 granules at a time. It is administered 2 times daily.
Claims (3)
1. A sorghum bran total flavone for inhibiting uric acid increase and preventing and treating gout diseases is characterized in that the sorghum bran total flavone is extracted and purified by the following method:
(1) extracting sorghum bran raw material with 35-50 deg.C warm water for 1-3 times, each time for 8-12 hr, filtering, collecting the extracted sorghum bran, extracting with 4-8 times of 60-90% ethanol containing 1-2% calcium oxide for 1-3 times, filtering, collecting ethanol extractive solution, decolorizing with 1-2% ethanol volume of activated carbon, and filtering to obtain ethanol extractive solution;
(2) taking the ethanol extract, passing through D101 macroporous adsorption resin treated by 60-90% ethanol in advance, eluting by 1-3 times of column volume by using 60-90% ethanol, collecting effluent and eluate, recovering ethanol, filtering, washing filter cakes with water, and drying to obtain the sorghum bran total flavonoids.
2. The sorghum bran total flavone for inhibiting uric acid increase and preventing and treating gout diseases according to claim 1 can be prepared into tablets, capsules, granules, powder and oral liquid according to the pharmacy requirement.
3. The use of sorghum bran total flavonoids according to claim 1 in the preparation of a medicament for inhibiting uric acid elevation and preventing and treating gout diseases.
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