CN106562985A - Medicinal health care applications of linarin - Google Patents
Medicinal health care applications of linarin Download PDFInfo
- Publication number
- CN106562985A CN106562985A CN201610989095.3A CN201610989095A CN106562985A CN 106562985 A CN106562985 A CN 106562985A CN 201610989095 A CN201610989095 A CN 201610989095A CN 106562985 A CN106562985 A CN 106562985A
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- China
- Prior art keywords
- linarin
- group
- diabetes
- mice
- blood glucose
- Prior art date
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Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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Abstract
The invention discloses medicinal health care applications of linarin, and in particular relates to the applications of linarin in preparing medicines, foods or health products for regulating blood glucose and blood lipid. The experimental result shows that linarin has the obvious effect of reducing blood glucose, and can improve sugar tolerance, improve the activity of superoxide dismutase of the bodies of diabetic mellitus mice, scavenge free radical, inhibit the lipid peroxidation effect, and reduce the content of malonaldehyde in the body; linarin can obviously reduce triglyceride and total cholesterol value, which indicates that linarin has a certain effect of reducing blood lipid; the preliminary experiment proves that linarin is low in toxicity and high in safety.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to the medicines and health protection purposes of linarin.
Background technology
Diabetes are a kind of global chronic diseases being characterized with hyperglycemia.Diabetes are in global sickness rate at present
Rise year by year, and become the chronic of the another impact human health being only second to after cardiovascular and cerebrovascular disease, tumor in the world
Disease.It is estimated to be within 2004 3400000 people and dies from diabetes, diabetes will becomes the seventh-largest cause of the death in the year two thousand thirty.2013 global
3.82 hundred million people be there are about with diabetes, wherein type 2 diabetes mellitus patient accounts for 90%, the number to diabeticss in 2035 is expected
5.92 hundred million will be risen to.National survey shows that more than 20 years old population diabetes totality prevalence of 2007-2008 China reaches
9.7%, rise to 11.6% within 2013, more than the 8.3% of the U.S., number reaches 1.14 hundred million, accounts for global diabetes patient's sum
1/3rd, current China has become the most country of global diabeticss number.The 1980's, diabetes mellitus in China are ill
Less than 1%, between 30 years, from rising violently 11.6% less than 1%, China is also patient of diabetes to Chinese adult diabetes prevalence to rate
One of fastest-rising country of sick rate.
" the diabetes mellitus in China society that diabetes branches of Chinese Medical Association in 2010 and International Diabetes Federation's joint are issued
Economic impact is studied " report claims, inland of China year Cost on Diabetes Mellitus Patients account for national medical treatment and always open up to 173,400,000,000 yuans
13% for propping up.Following 10 to 20 years, this numeral also quickly will rise.This is diagnosed as China there are about 50,000,000
Patient, may occur the complication such as apoplexy, blind and kidney disease when its discovery is ill.The medical expense of diabeticss
It is 9 times of same sex non-diabetic person of the same age, the spending of the course of disease patient medical of more than 10 years is higher 4.6 times than the patient of 1 to 2 year,
In its family income, 22% is used for treating diabetes.
Diabetes are a kind of commonly encountered diseases, or a kind of life-long disease, it is difficult to thoroughly cure, need Long-term taking medicine, diabetes
The public health problem of serious harm human health is become.
Diabetes are divided into type 1 diabetes, type 2 diabetes mellitus and gestational diabetes three types.Type 1 diabetes, are also called pancreas
Island element dependent diabetes, account for the 10% of diabetic sum, often betide Children and teenager, but can also betide and appoint
What, the cause of disease are to be subject to cell-mediated autoimmune destruction due to B cell at age, and itself can not synthesize and secrete islets of langerhans
Element, its treatment rely primarily on injection of exogenous insulin.Type 2 diabetes mellitus, are also called non-insulin-dependent diabetes mellitus, account for sugar
The 90% of the sick patient's sum of urine, after 35 years old, onset is slow, concealment, and some patients are in physical examination for age of onset majority
Or find when checking other diseases, mainly caused by insulin resistant and impaired insulin secretion.Gestational diabetes refer in gestation
The diabetes that mid-term or later stage find, after mid trimester of pregnancy, especially in latter half of gestation, placenta secretion is various to glucagon
Hormone, such as galactagogin etc., and Insulin receptor INSR quantity is reduced on target cell membrane, 50%～70% gestational diabetes
Type 2 diabetes mellitus are shown as after childbirth, a part of patient's carbohydrate tolerance recovers normal, and only individuals patients are changed into type 1 diabetes.
If diabetes are treated not in time, persistent high blood sugar and long-term metabolic disorder etc. can cause body tissue's organ, especially
It is the infringement and its dysfunction and exhaustion of eye, kidney, cardiovascular and nervous system.Severe patient can cause dehydration, electrolyte disturbance
With acute complicationses ketoacidosiss and the Hyperosmotic coma such as acid base imbalance.The treatment of diabetes, it is not sugar to reduce blood glucose
The sole purpose of urine disease treatment, while effective control blood glucose, prevents and reduces various complication, improve minimal invasive treatment's matter
Amount, extends patient vitals and is only final goal.
Type 2 diabetes mellitus account for more than the 90% of diabetes number, are the emphasis for the treatment of diabetes.Clinical conventional treatment at present
Type 2 diabetes mellitus medicine mainly includes sulphanylureas, biguanideses, alpha-glucosidase inhibitor, euglycemic agent and insulin etc.
Medicine, these medicines have certain side effect, such as hypoglycemia, intestinal tympaniteses, cardiovascular danger etc..Exploitation Small side effects, to 2 types sugar
The blood sugar lowering that urine disease and its complication have multiple treatments effect has important clinical value.
Linarin, also known as robinin.Modern pharmacology research shows that linarin plays the role of anti-inflammatory and antalgic, can suppress scorching
Disease mediation plain class such as tumor necrosis factor (TNF), the expression of interleukin (IL).The hypoglycemic activity of linarin is had no at present
Document report.
The content of the invention
It is an object of the invention to provide the medicines and health protection purposes of a kind of new application of linarin, specifically linarin.
The technical solution adopted in the present invention is, linarin in hypoglycemic drug or food or health product is prepared should
With.
Linarin is preparing blood lipid-lowering medicine or food or the application in health product.
The dosage form of medicine is oral or injection type.
Linarin can reduce hyperglycemia mouse blood sugar, while it is little to improve the carbohydrate tolerance of diabetic mice, reduction diabetes
The content of Mus Serum MDA, T-CHOL and triglyceride, and have no toxic side effect, therefore linarin can be used for diabetes, height
The related medicine of blood fat, food or food and pharmaceutical composition.
The dosage form of the medicine or product is oral capsule, tablet and other dosage forms such as pill, drop pill, granule
Agent, oral liquid, injection etc..
Specific embodiment
The present invention is further explained with reference to embodiment, following examples are only used for explaining of the invention, and not
It is to limit the scope of the invention.
The preparation of 1 Flos Buddlejae glycosides capsule of embodiment
Preparation method：By above-mentioned each composition mix homogeneously, sky hard capsule is filled in, is obtained final product.
The preparation (one) of 2 linarin tablet of embodiment
Preparation method：Linarin is mixed with starch, plus starch slurry makes suitable soft material in right amount, is pelletized with 14 mesh sieves, in 60-
70 DEG C of dryings, granulate, tabletting after adding dried starch, magnesium stearate to mix are obtained final product.
The preparation (two) of 3 linarin tablet of embodiment
Preparation method：Above composition mix homogeneously, tabletting are obtained final product.
The preparation of 4 linarin granule of embodiment
Linarin 20g
Soluble starch 979.5g
Stevioside 0.5g
Preparation method：Above composition mixes, and makees wetting agent with 60% appropriate amount of ethanol, pelletizes, and is dried, granulate, packaging, i.e.,
.
The preparation of 5 linarin drop pill of embodiment
Linarin 20g
Polyethylene glycol 6000 180g
Preparation method：Polyethylene glycol 6000 heating fusing, adds linarin stirring and dissolving, is incubated 65-75 DEG C, uses pill dripping machine
Pelletization is condensed in instilling liquid paraffin or methyl-silicone oil, is obtained final product.
The preparation of 6 Flos Buddlejae glucoside oral liquid of embodiment
Preparation method：Linarin, stevioside and sorbic acid add stirring and dissolving in purified water, filter, and embedding is in 10ml mouths
Take in liquid bottle, 100 DEG C of flowing steam sterilizations 30 minutes are obtained final product.
The preparation of 7 Flos Buddlejae glycoside injection liquid of embodiment
Linarin 10g
Sodium Chloride 7g
Water for injection adds to 1000ml
Preparation method：Linarin, Sodium Chloride add stirring and dissolving in water for injection, filter, in embedding ampoule, 100 DEG C of streams
Logical steam sterilization 30 minutes, obtains final product.
Further illustrate the beneficial effect produced by the present invention below from the pharmacological results：
Linarin blood sugar lowering, hypolipidemic activity are determined
Mice hyperglycemia model is set up with streptozotocin (Streptozotocin, STZ) lumbar injection, gavage is given respectively
Give doses linarin, determine blood glucose, observe its hypoglycemic activity, and determine Triglycerides in Serum and T-CHOL contains
Amount.
1. medicine and preparation of reagents
The preparation of citric acid-sodium citrate buffer：Precision weighs citric acid 2.100g, is dissolved in 100ml distilled water
In, precision weighs sodium citrate 2.900g, is dissolved in 100ml distilled water, and citric acid solution and sodium citrate solution are pressed 1:
1.32 are made into the solution (matching while using) that pH value is 4.4, degerming with 0.22um filter membranes, standby.
The preparation of 10mg/ml streptozotocin (Streptozotocin, STZ) solution：Streptozotocin one
(100mg), adding citric acid-sodium citrate buffer is to 10ml, shake up (this operation is carried out on ice chest, and lucifuge, institute
It is finished in 30min with solution).
2. preliminary toxicity test
To ensure Drug safety under test dose, preliminary toxicity test is carried out.Take mice 3, gavage linarin
200mg/kg, observes 24 hours, it is found that mice does not have dead generation and activity is normal, illustrate that dosage up to 200mg/kg is
Safety.The concentration of the high, medium and low dosed administration group of experimental group linarin is respectively set to 100mg/kg, 50mg/kg, 25mg/
Kg, experiment is carried out under the dosage to be guaranteed without animal dead.
3. experimental technique and result
3.1 streptozotocin inducing mouse experimental hyperglycemia models
Body weight is about the kunming mice 80 of 20g health, and after adaptability is raised three days, taking 70 mices daily morning gives
Lumbar injection concentration is the STZ solution of 10mg/ml, injects 50mg/kg daily by body weight, continuous injection 3 days.Matched group 10 is little
Mus, the citric acid-sodium citrate buffer of daily lumbar injection equivalent.Mice drinking public water supply, raises with mice conventional sterilant
Feedstuff.After daily observation drinking-water meal situation, modeling 3 one weeks, tail vein blood surveys fasting glucose (after fasting can't help water 6 hours),
Mice of the blood glucose value more than 11.1mmol/L is selected as experimental diabetic animal models.
3.2 experimental administration schemes
Hyperglycemia mice is divided into into 5 groups according to blood glucose height, respectively model group, positive drug group, linarin are high, medium and low
Dosage group, takes normal mouse for blank control group, 10 per group.Wherein administration group gavage 100mg/kg, 50mg/kg and 25mg/
Kg, positive administration group mouse stomach metformin hydrochloride 200mg/kg, blank group and model group mouse stomach distilled water, each group are equal
Continuous gavage is administered 15d.
The measure of 3.3 fasting glucose
After mice continuous gavage 15d, the equal fasting of each group can't help water 6 hours, and subsequent tail vein takes blood, determine empty with blood glucose meter
Abdomen blood glucose value, the results are shown in Table 1.
1 each experimental mice blood sugar level of table
Note:Compare with model control group, * * P<0.01, * P<0.05.
After mice is modeled one week with STZ, mice mean blood glucose concentrations are significantly raised.There are 65 mices in 70 kunming mices
Blood sugar concentration be more than 11.1mmol/L, meet the requirement of diabetic mice, that is, model successfully.Successive administration mice sky after 15 days
As shown in table 1, wherein linarin high dose group, middle dose group fasting blood sugar are substantially less than diabetic model group to abdomen blood sugar concentration
(P<0.05)；Low dose group fasting blood sugar compares with diabetic model group that there was no significant difference (P>0.05).
After modeling, normal group Mouse Weight increases fast, and diet drinking-water urine volume is normal, and bright, fur is smooth, and comparison is clever
It is living.Model group mice polydipsia polyphagia polyuria symptom substantially, loses weight, and fur erects matt, lethargy, bradykinesia,
Linarin administration group mice ordinary circumstance is better than model group, and wherein high dose administration group mice integral status are preferable, many drinking water copiously
Food polyuria symptom mitigation, also no model group declines soon body weight, and in order, fur is neatly more glossy for positive drug group mice,
Activeness is good.
The measure of 3.4 carbohydrate tolerance (OGTT)
On the feed after the staple food such as rice, face or oral glucose, almost all is made blood sugar concentration liter by intestinal absorption to normal person
Height, stimulate insulin secretion, liver glycogen synthesis increase, glycogen output reduce, in-vivo tissue to glucose utilization increase, therefore,
Highest blood glucose is usually no more than 10mmol/L after meal, and how much blood glucose of taking food is held in a more stable scope.This
Illustrate that normal person is very strong to glucose ground tolerance, i.e. Normal glucose tolerance.Carbohydrate tolerance experiment is a kind of oral glucose
Load test, to understand human body to the blood sugar regulation ability after glucose load.Tested by OGTT, can be with early discovery sugar
Developmental and Metabolic Disorder early diagnosiss diabetes.
After mice continuous gavage 15d, fasting can't help water 6 hours, and detection fasting blood sugar is subsequently pressed as blood glucose value when zero
3g/kg dosage gavages give each group mouse glucose solution, and after gavage, 0.5h, 1h and 2h determine mouse blood sugar value respectively, see
Each experiment mice change of blood sugar situation is examined, 2 are the results are shown in Table.
2 each experimental mice carbohydrate tolerance of table
Note:Compare with model control group, * * P<0.01, * P<0.05.
Normal group mouse blood sugar is rapid after gavage gives 3g/Kg glucose 0.5h to be raised and peaking, and blood glucose is opened later
Begin to decline.Model group mouse blood sugar is persistently raised after glucose load, though decrease in 2h, with glucose load before blood sugar concentration phase
Than changing greatly.Linarin middle and high dosage group 0.5h peakings after glucose load, blood glucose rise amplitude are significantly less than model
Group, is reduced to after 2h before glucose load near blood sugar level, and comparing with model group blood glucose has significant difference (P<0.05), show to cover
Flower glycosides has improvement result to the carbohydrate tolerance of diabetic mice.
The measure of 3.5 each group mice superoxide dismutase (SOD) vigor
Free radical can cause various unsaturated fatty acid peroxidating and generate lipid peroxide (LPO), and which finally produces third
Dialdehyde, crosslinks can protein, nucleic acid, lipid, make biomembrane that degeneration, cell mutation, aging or death to occur.In vivo
Superoxide dismutase (SOD) is the enzyme for directly removing free radical, can block free radical, promotes to produce the chain reaction of LPO, so as to
Cell is protected not damaged by free radical, research shows that blood glucose rise has direct relation with the lipid peroxidation that free radical causes.
Second day after detection carbohydrate tolerance, after can't help water six hours to each group mice fasting, gastric infusion records the time,
And pluck eyeball in gastric infusion one hour after and take blood, 30min, 3500r/min centrifugation 10min are stood, serum is rapidly separated.It is above-mentioned
Serum, xanthine oxidase determine activity of SOD in serum, the results are shown in Table 3.
3 each experimental mice SOD value of table
Note:Compare with model control group, * * P<0.01, * P<0.05.
Linarin high dose group, middle dose group SOD are all remarkably higher than diabetic model group (p<0.05)；Low dose group SOD
Though raising, compare with model group without significant difference (p>0.05), illustrate that linarin can improve diabetic mice body SOD work
Property.
The measure of 3.6 each group mice mda contents
Malonaldehyde is the important indicator of the indirect reaction body free radical level of production and body lipid Petoxidation situation,
The important indicator of lipid mechanism harm is also considered as simultaneously.Above-mentioned serum, using thiobarbituricacidα- colorimetric method for determining serum the third two
Aldehyde, the results are shown in Table 4.
4 each experimental mice MDA of table
Note:Compare with model control group, * P<0.01.
Linarin high dose group, middle dose group MDA pole is substantially less than diabetic model group (p<0.01)；Low dose group
Though MDA is less than model group, no significant difference (p>0.05).Illustrate that linarin can reduce diabetic mice body serum
MDA values.
The measure of 3.7 each groups mice triglyceride (TG) and T-CHOL (CHOL)
Diabetes are often accompanied by disorders of lipid metabolism, and during blood circulation, FFA concentrations are too high, and in cell
The interior inner lipid content such as beta Cell of islet, myocyte and stem cell excessively easily causes the 2 of diabetes, particularly insulin resistant
Patients with type Ⅰ DM.Above-mentioned serum, determines test kit using triglyceride and T-CHOL, detects Triglyceride values and total gallbladder on an empty stomach
Sterin value, the results are shown in Table 5.
The TG and CHOL of 5 each experimental mice of table
Note:Compare with model control group, * P<0.01.
Linarin is high, middle dose group TG is write less than diabetic model group (p<0.05), though low dose group TG has reduction,
There was no significant difference compared with model group (p>0.05).Illustrate that linarin can reduce diabetic mice body serum TG value.
High, medium and low dosage group CHOL of linarin pole is substantially less than diabetic model group (p<0.01), blank group CHOL
Pole is substantially less than model group (p<0.01).Illustrate that linarin can reduce diabetic mice body serum CHOL.
4. experiment conclusion
, compared with model control group, experimental group (middle and high dosage group) is Jing after linarin treatment, empty for experimental group fasting blood sugar
Abdomen blood glucose is significantly reduced, and shows that linarin has good blood sugar reducing function to diabetic mice, and linarin is to diabetic mice
Carbohydrate tolerance improve significantly.This experiment detects that Content of MDA and SOD Activity Results show, experiment is high, middle dosage
The activity of SOD in serum of group substantially increases, and Content of MDA is significantly reduced, and illustrates that linarin can improve diabetic mice body
SOD is active, removes free radical, and anti-lipid peroxidation effect, reduces the content of internal malonaldehyde；This experiment detects serum
CHOL and TG content results show that linarin administration group can significantly reduce CHOL, and TG values make the CHOL values and TG of diabetic mice
Value recovers normal.
This experiment shows that linarin hypoglycemic activity is raised with the increase of dosage, illustrates the hypoglycemic activity of linarin
With dose dependent；The T-CHOL of linarin administration group is reduced with triglyceride simultaneously, illustrates that linarin also has one
Fixed effect for reducing blood fat；Preliminary experiment shows that linarin toxicity is low, safe.
Claims (3)
1. linarin is preparing hypoglycemic drug or food or the application in health product.
2. application according to claim 1, it is characterised in that linarin is preparing blood lipid-lowering medicine or food or health product
In application.
3. application according to claim 1 and 2, it is characterised in that the dosage form of medicine is oral or injection type.
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