CN108245551A - A kind of pharmaceutical composition for preventing insulin resistance relevant disease and preparation method thereof - Google Patents
A kind of pharmaceutical composition for preventing insulin resistance relevant disease and preparation method thereof Download PDFInfo
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- CN108245551A CN108245551A CN201810178971.3A CN201810178971A CN108245551A CN 108245551 A CN108245551 A CN 108245551A CN 201810178971 A CN201810178971 A CN 201810178971A CN 108245551 A CN108245551 A CN 108245551A
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- 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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- A—HUMAN NECESSITIES
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- 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
- A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
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Abstract
The invention discloses a kind of pharmaceutical composition for preventing insulin resistance relevant disease, the components for preparing raw material and including following mass percentage of described pharmaceutical composition：Cortex Cinnamomi volatile oil 10~90% and berberine 10~90%.The invention also discloses the preparation methods of aforementioned pharmaceutical compositions.The pharmaceutical composition of the present invention selects Cortex Cinnamomi volatile oil and berberine phase 5, the two brings out the best in each other, it can obviously reduce insulin resistance index, increase insulin sensitivity detection index, effectively reduce in dextrose tolerance test area (AUC) under glucose curve, weight gain and Fat Accumulation caused by reducing insulin resistance reduce blood glucose level and improve insulin resistance, available for the disease that prevention insulin resistance is pathophysiological basis；Not only flavour of a drug are less, are conducive to quality control, and medicine letter power is special, and prevention insulin resistance is also very notable for the effect of the disease of pathophysiological basis.
Description
Technical field
The present invention relates to the drug for the treatment of diabetes, especially a kind of pharmaceutical composition for preventing insulin resistance relevant disease
Object and preparation method thereof.
Background technology
Insulin resistance (Insulin resistance, IR) refers to that the biological effect of insulin in blood reduces, i.e. machine
Hypoergic a kind of state that body acts on the biological regulation of insulin, insulin promote glucose uptake effect impaired,
Compensatory insulin secretion is caused to increase, important symbol is hyperinsulinemia, is embodied in peripheral tissues to insulin
Sensibility declines and the Use barriers to glucose.Insulin resistance is the common pathologic, physiologic of the numerous diseases of metabolic syndrome
Basis, such as obesity, hyperglycemia, diabetes B, hyperlipemia, coronary heart disease, hypertension, atherosclerotic coronary heart disease.
According to statistics, the obese patient more than 1,000,000,000, more than 80% shows apparent IR to world's obese people quantity；And 2 types are sugared
The crowd of urine disease has also reached incidences of 1.5 hundred million, the IR in diabetes B patient and has been up to 85% or so.More have been reported that discovery
Gravid woman's insulin sensitivity declines 50%, easily suffers from insulin resistance.Therefore, how to alleviate insulin resistance, improve pancreas
The sensibility of island element has become the diseases such as prevention obesity, diabetes B, hypertension, hyperlipidemia, atherosclerotic coronary heart disease
Important topic.
The molecular mechanism that insulin resistance generates not yet illustrates completely at present, and a large amount of research has shown that, insulin resistance
Occur to swash with phosphatidylinositols -3- hydroxyls kinases (phosphatidylinositol 3-hydroxy kinase, PI3K)/albumen
Enzyme B (Protein Kinase B, PKB) insulin signaling pathway is obstructed, (the glucose transporter of glucose transporter 4
4, GLUT4) transposition is abnormal, -3 β of Glycogen synthesis kinases (glycogen synthase kinase-3 β, GSK-3 β) is activated, cell
Extracellular signal-regulated kinase activity reduction etc. is closely related.PI3K/PKB accesses are the main ways that insulin plays hypoglycemic effect
Diameter.The treatment of clinicing aspect IR is still the control for its one-sided symptom, treated with insulin sensitizer based on, such as thiophene
Oxazolidinedione class increases utilization of the peripheral tissues to glucose.It is equipped with for the hypoglycemic medicine of hyperglycemia or for hypertension
Antihypertensive drugs etc., link is cumbersome, of high cost, and side effect is big, there is no simple and effective comprehensive means of prevention.And Western medicine drug meeting
Tolerance is generated, dosage constantly increase is until failure.Finding therapy simple and effective, that multiple target point is comprehensive becomes urgent
Being essential will.
Motherland's medicine thinks that insulin resistance is mostly asthenia in origin and asthenia in superficiality, and Kidney-Yang deficiency is it, and wind, fire, phlegm, the stasis of blood are marked for it.
Kidney-Yang deficiency, the high Sheng of endogenous fire, breakdown of the normal physiological coordination between the heart and the kidney are its main pathogenesis, treat the method that ought be purged heat with yang-tonifying.The active constituent coptis of the coptis
Element, there is clearing away the heart-fire, and soothing the liver fire rushes down spleen fire, drops lung-fire, gentle the five internal organs.The active constituent Cortex Cinnamomi volatile oil of Chinese cassia tree is rich sweet pungent big
Heat, in lower walking, guiding fire to origin strengthens the sun of the gate of vitality, and the gas of plant heart kidney, a surname leads hundred medicines, without being avoided out of fear, makes sun length is then cloudy to disappear certainly,
And all card self-healing.The cold heat of two medicines one, monoyin and monoyang are linked up up and down, and regulation between water and fire can across-the-board regulation human body energy.This medicine
Compositions are according to the pathogenesis of insulin resistance and the pathogenesis of modern medicine, according to the dialectical and logos group of the traditional Chinese medical science
Side with the active constituent berberine of the modern pharmaceutical technique extraction coptis and the active constituent Cortex Cinnamomi volatile oil of Chinese cassia tree, optimizes
Combination obtains the drug of effectively prevention insulin resistance relevant disease.It is tried through zoopery, cell experiment and randomized controlled clinical
Verify bright, which can significantly be effectively improved the clinical symptoms and lab index of insulin resistance relevant disease.It prepares
Medicinal material used in pharmaceutical composition of the present invention is common medicinal material, and moderate, material is easy to get, and preparation process is simple, suitable for production
Industry metaplasia is produced.
Lu Ting【1】Report Cortex Cinnamomi volatile oil extract helps to improve diabetes B patient blood glucose, glycosylated hemoglobin
(HbA1c) and triacylglycerol (TG) is horizontal, and has no adverse reaction.Using the method for randomized double-blind, patient is divided into two groups (two groups
Gender, age take Gliclazide sustained-release tablet amount, BMI no significant differences) it is tested, as a result prompt Chinese cassia tree volatilization
Oily group can obviously improve the HbA1c of IR patient, fasting blood-glucose (FBG) and TG compared with placebo, and difference has statistical significance.
He Jinting【2】Think that berberine has blood pressure lowering, anti-arrhythmia, platelet aggregation, anti-oxidant and removing is inhibited to live
Free love base, resist myocardial ischemia, relaxing smooth muscle, cardiac stimulant, anticancer, to the protection of cerebral ischemia, improve acute lung injury and
The pharmacological actions such as pulmonary fibrosis, CNS inhibition, hypoglycemic, clinical practice are extensive.
The patent application of Publication No. CN1364610A discloses a kind of pure Chinese medicinal preparation blood-sugar reducing tea for treating diabetes, is
By radix polygonati officinalis, pueraria lobata, Radix Astragali, Chinese yam, pumpkin, balsam pear, soya bean, Chinese gall, green tea, Pogostemon cablin, mantis egg-case, garlic, Radix Glycyrrhizae, flower
Powder, berberine, tea bag made of Cortex Cinnamomi volatile oil.Although drug described in the patent application includes the coptis, two taste of Chinese cassia tree
Chinese medicine, but not only prescription is big for the drug, medicinal material up to 16 tastes, and the pharmacological property overlapping of drug, pharmacological mechanism is unclear, cost
It is higher with security risk, it is unfavorable for effective quality control and production.
Bibliography：
1st, it is big to contain influence [J] Jiangsu of the macro smooth Cortex Cinnamomi volatile oils extract to diabetes B patient's fasting blood-glucose by Lu Ting
Learn journal (medicine) .2013 (1)：46-48；
2nd, modern clinic application Changchun University of Traditional Chinese Medicine journal of He Jinting, Yu Shun berberines, 2012 (03):544-
Page 546；
3rd, HananS.El-Abhar1, Mona F, et al, Topiramate-induced modulation of
hepatic molecular mechanisms:An aspect for its anti-insulin resistant effect
[J] .PLoS One, 2012,7 (5):e37757.
Invention content
Based on this, it is an object of the invention to overcome in place of above-mentioned the deficiencies in the prior art and pancreas islet can be prevented by providing one kind
Element resists the pharmaceutical composition of relevant disease, and flavour of a drug are few, curative for effect.
To achieve the above object, the technical solution taken of the present invention is：
As the first aspect of the invention, the present invention provides a kind of medicine groups for preventing insulin resistance relevant disease
Close object, the component for preparing raw material and including following mass percentage of described pharmaceutical composition：10~90% He of Cortex Cinnamomi volatile oil
Berberine 10~90%.In addition, the pharmaceutical composition can include medically acceptable auxiliary material.Preferably, the drug
Granule, pill, tablet or capsule can be made in composition.
Preferably, preparing in raw material when the pharmaceutical composition of the present invention, the mass percentage of Cortex Cinnamomi volatile oil is 10
~90%, when the mass percentage of berberine is 10~90%, it can preferably inhibit weight gain caused by insulin resistance.
Preferably, the component for preparing raw material and including following mass percentage：Cortex Cinnamomi volatile oil 25% and berberine
75%.When the preparing the component that aforementioned proportion is included in raw material of pharmaceutical composition of the present invention, inhibiting insulin resistance
Caused weight gain reduces insulin level, mitigates insulin resistance, increases the ability of four aspects of insulin sensitivity most
It is good.
Preferably, the component for preparing raw material and including following mass percentage：Cortex Cinnamomi volatile oil 50% and berberine
50%.Present inventor has found through test of many times, when the preparing for pharmaceutical composition of the present invention includes above-mentioned ratio in raw material
During the component of example, inhibiting weight gain caused by insulin resistance, reducing insulin level, mitigation insulin resistance, increasing
Add the ability of four aspects of insulin sensitivity more preferably.
Preferably, the insulin resistance relevant disease is obesity, diabetes, hyperlipidemia, metabolic syndrome or high blood
Pressure etc..
Preferably, the Cortex Cinnamomi volatile oil extracts from Lauraceae aiphyllium plant Chinese cassia tree (Cinnamomum cassia
Presl dry hide) or/and thick branch skin；The berberine extracts from the Chinese medicine Huang for belonging to Ranunculaceae, Coptis herbaceos perennial
Even (Coptis chinensis Franch.).
As the second aspect of the invention, the present invention also provides the preparation method of aforementioned pharmaceutical compositions, the system
Preparation Method includes the following steps：
(1) Chinese cassia tree is taken to extract, obtains Cortex Cinnamomi volatile oil extract；Beta-cyclodextrin and purified water are taken, in boiling water bath
It is heated to dissolving, treats that temperature is down to 25~50 DEG C, after constant temperature stirs 15~30 minutes, Cortex Cinnamomi volatile oil extract is slowly injected into
In the beta-cyclodextrin, continue constant temperature stirring 30~take out after sixty minutes, be cooled to 25 DEG C, rapid filtration under suction, washing, drying, i.e.,
Obtain the inclusion compound of Cortex Cinnamomi volatile oil extract；
(2) coptis is taken to crush, after sieving, alcohol reflux extraction adds in the acetic acid that mass concentration is 1% and dissolves by heating, so
Afterwards until enriching hydrochloric acid to solution muddiness, cooling is placed, that is, has berberine hydrochloride to salt out, gained crystallization ice water, acetone are first
After wash, obtain berberine crude product；Into gained berberine crude product plus dissolving is boiled in distilled water, heating, and it is 8.5 to adjust PH with milk of lime
~9.8, filtrate is placed into cooling acidification, that is, has needle-shaped coptis cellulose crystal to be precipitated, by gained coptis cellulose crystal at 50~60 DEG C
Drying, obtains the berberine fine work of more than 95% mass concentration；
(3) inclusion compound of the Cortex Cinnamomi volatile oil extract and the berberine fine work are mixed, adds in various dosage form institutes
The auxiliary material needed is up to described pharmaceutical composition.
It should be noted that described pharmaceutical composition adds in appropriate auxiliary material, any conventional oral preparation shape can be made
Formula；Specifically, drug or health products made of the composition of the present invention can be granule, it is tablet, freeze-dried powder, capsule, sublingual
Lozenge or other suitable shapes, specific preparation method can refer to《Chinese Pharmacopoeia (2015 editions)》Production method.
Preferably, the weight of the beta-cyclodextrin is the 10~20% of the Cortex Cinnamomi volatile oil weight.
Preferably, Cortex Cinnamomi volatile oil uses carbon dioxide supercritical extraction method or steam distillation in the step (1)
Extraction, obtains Cortex Cinnamomi volatile oil extract.
In conclusion beneficial effects of the present invention are：
(1) pharmaceutical composition of the invention selects Cortex Cinnamomi volatile oil and berberine phase 5, and the two brings out the best in each other, and can significantly drop
Low insulin resistance index (insulin resistance index, HOMA-IR) increases insulin sensitivity detection index
(quantitative insulin sensitivity check index, QUICKI), effectively reduces dextrose tolerance test
Area (AUC) under middle glucose curve reduces weight gain and Fat Accumulation caused by insulin resistance, reduces blood glucose level simultaneously
Improve insulin resistance, available for the disease that prevention insulin resistance is pathophysiological basis；
(2) present invention is made of Cortex Cinnamomi volatile oil extract and berberine water extract, and not only flavour of a drug are less, are conducive to quality
Control, and it is also very notable for the effect of the disease of pathophysiological basis to prevent insulin resistance；
(3) and the pharmaceutical composition of the present invention be using modern pharmaceutical technique the extraction coptis and Chinese cassia tree chief active into
Point, and optimize, clinical practice is convenient, has apparent superiority.
Description of the drawings
Fig. 1 is influence result figure of the Chinese herbal compounds of the present invention to insulin resistant mice glucose tolerance；
Fig. 2 is influence result figure of the Chinese herbal compounds to insulin resistant model cell PI3K protein expressions.
Specific embodiment
The present invention is more fully understood for the ease of the public, it is specific real below by embodiment, effect experiment, contrast test etc.
The advantageous effect for applying mode to further illustrate the present invention.
Embodiment 1
1st, a kind of embodiment of the pharmaceutical composition of prevention insulin resistance relevant disease of the invention, the pharmaceutical composition
The raw material for preparing of object includes following components：Cortex Cinnamomi volatile oil 50g, berberine 50g.
2nd, the preparation method of aforementioned pharmaceutical compositions：
(1) Cortex Cinnamomi volatile oil carbon dioxide supercritical extraction method or extraction by steam distillation are taken, obtains Chinese cassia tree volatilization
Oil extract；Beta-cyclodextrin is weighed by the 15% of Cortex Cinnamomi volatile oil weight, is put in container, adds in purified water, boiling water bath heating makes
It is dissolved, and is placed to 50 DEG C, and after constant temperature stirs 30 minutes, Cortex Cinnamomi volatile oil extract is slowly injected into beta-cyclodextrin, is continued permanent
Temperature stirring is taken out after 50 minutes, is cooled to 25 DEG C, and rapid filtration under suction is first used after being rinsed with a small amount of water, then washed with ether, dry,
Up to the inclusion compound of Cortex Cinnamomi volatile oil extract；
(2) take the coptis crush, sieving after, alcohol reflux extraction, under reduced pressure in the case of steam ethyl alcohol (recycling) until palm fibre
Red syrup shape adds mass concentration and is dissolved by heating for 1% acetic acid, filters and remove insoluble matter, be then added dropwise in solution dense
Until hydrochloric acid to solution muddiness, cooling is placed, that is, the berberine hydrochloride for there are yellow needles salts out, and filters, and gained crystallization is used
Ice water washes twice, then washed once with acetone, obtains berberine crude product；Add distilled water to berberine crude product, heating is boiled to firm
Good dissolving, it is 8.5 to adjust PH with milk of lime, slightly cold rear elimination impurity, and continues filtrate placing cooling acidification, that is, has needle-shaped crystalline substance
Body berberine is precipitated, and filtering dries berberine crystalline solid at 50 DEG C, obtains berberine fine work, the Huang of this method extraction
Even cellulose content is 95% (mass concentration)；
(3) inclusion compound of Cortex Cinnamomi volatile oil extract and berberine fine work are mixed, adds in appropriate auxiliary material, obtain institute
The pharmaceutical composition stated.
Embodiment 2
1st, a kind of embodiment of the pharmaceutical composition of prevention insulin resistance relevant disease of the invention, the pharmaceutical composition
The raw material for preparing of object includes following components：Cortex Cinnamomi volatile oil 34g, berberine 66g.
2nd, the preparation method of aforementioned pharmaceutical compositions：
(1) Cortex Cinnamomi volatile oil carbon dioxide supercritical extraction method or extraction by steam distillation are taken, obtains Chinese cassia tree volatilization
Oil extract；Beta-cyclodextrin is weighed by the 12% of Cortex Cinnamomi volatile oil weight, is put in container, adds in purified water, boiling water bath heating makes
It is dissolved, and is placed to 37 DEG C, and constant temperature stirs after twenty minutes, and Cortex Cinnamomi volatile oil extract is slowly injected into beta-cyclodextrin, is continued permanent
Temperature stirring is taken out after 35 minutes, is cooled to 25 DEG C, and rapid filtration under suction is first used after being rinsed with a small amount of water, then washed with ether, dry,
Up to the inclusion compound of Cortex Cinnamomi volatile oil extract；
(2) coptis is taken to crush, after sieving, alcohol reflux extraction adds in mass concentration and dissolved by heating for 1% acetic acid, then
Until enriching hydrochloric acid to solution muddiness, cooling is placed, that is, has berberine hydrochloride to salt out, gained crystallization ice water, acetone are successively
Washing, obtains berberine crude product；Distilled water heating is added to boil dissolving to berberine crude product, it is 8.7 to adjust PH with milk of lime, and filtrate is put
Cooling acidification is put, that is, has the precipitation of acicular crystal berberine, berberine crystalline solid at 51 DEG C is dried, obtains 95% (matter of content
Measure concentration) berberine fine work；
(3) inclusion compound of Cortex Cinnamomi volatile oil extract and berberine fine work are merged into mixing, adds in appropriate auxiliary material, obtain
To the pharmaceutical composition.
Embodiment 3
1st, a kind of embodiment of the pharmaceutical composition of prevention insulin resistance relevant disease of the invention, the pharmaceutical composition
The raw material for preparing of object includes following components：Cortex Cinnamomi volatile oil 66g, berberine 34g.
2nd, the preparation method of aforementioned pharmaceutical compositions：
(1) Cortex Cinnamomi volatile oil carbon dioxide supercritical extraction method or extraction by steam distillation are taken, obtains Chinese cassia tree volatilization
Oil extract；Beta-cyclodextrin is weighed by the 13% of Cortex Cinnamomi volatile oil weight, is put in container, adds in purified water, boiling water bath heating makes
It is dissolved, and is placed to 40 DEG C, and after constant temperature stirs 25 minutes, Cortex Cinnamomi volatile oil extract is slowly injected into beta-cyclodextrin, is continued permanent
Temperature stirring is taken out after forty minutes, is cooled to 25 DEG C, and rapid filtration under suction is first used after being rinsed with a small amount of water, then washed with ether, dry,
Up to the inclusion compound of Cortex Cinnamomi volatile oil extract；
(2) coptis is taken to crush, after sieving, alcohol reflux extraction adds in mass concentration and dissolved by heating for 1% acetic acid, then
Until enriching hydrochloric acid to solution muddiness, cooling is placed, that is, has berberine hydrochloride to salt out, gained crystallization is successively with ice water, acetone
Washing, obtains berberine crude product；Berberine crude product is added into distilled water, dissolving is boiled in heating, and it is 8.8 to adjust PH with milk of lime, by filtrate
Cooling acidification is placed, that is, has the precipitation of acicular crystal berberine, berberine crystalline solid at 52 DEG C is dried, obtains berberine fine work
(mass concentration 96%)；
(3) inclusion compound of Cortex Cinnamomi volatile oil extract and berberine fine work are merged into mixing, adds in appropriate auxiliary material, obtain
To the pharmaceutical composition.
Embodiment 4
1st, a kind of embodiment of the pharmaceutical composition of prevention insulin resistance relevant disease of the invention, the pharmaceutical composition
The raw material for preparing of object includes following components：Cortex Cinnamomi volatile oil 25g, berberine 75g.
2nd, the preparation method of aforementioned pharmaceutical compositions：
(1) Cortex Cinnamomi volatile oil carbon dioxide supercritical extraction method or extraction by steam distillation are taken, obtains Chinese cassia tree volatilization
Oil extract；Beta-cyclodextrin is weighed by the 14% of Cortex Cinnamomi volatile oil weight, is put in container, adds in purified water, boiling water bath heating makes
It is dissolved, and is placed to 45 DEG C, and after constant temperature stirs 30 minutes, Cortex Cinnamomi volatile oil extract is slowly injected into beta-cyclodextrin, is continued permanent
Temperature stirring is taken out after 45 minutes, is cooled to 25 DEG C, and rapid filtration under suction is first used after being rinsed with a small amount of water, then washed with ether, dry,
Up to the inclusion compound of Cortex Cinnamomi volatile oil extract；
(2) coptis is taken to crush, after sieving, alcohol reflux extraction adds in mass concentration and dissolved by heating for 1% acetic acid, then
Until enriching hydrochloric acid to solution muddiness, cooling to be placed, that is, has berberine hydrochloride to salt out, gained crystallization ice water, acetone wash,
Obtain berberine crude product；Add distilled water to berberine crude product, dissolving is boiled in heating, and it is 8.9 to adjust PH with milk of lime, filtrate is placed cold
But it is acidified, that is, has the precipitation of acicular crystal berberine, berberine crystalline solid at 53 DEG C is dried, obtains berberine fine work (quality
It is a concentration of 96%)；
(3) inclusion compound of Cortex Cinnamomi volatile oil extract and berberine fine work are merged into mixing, adds in appropriate auxiliary material, obtain
To the pharmaceutical composition.
Embodiment 5
1st, a kind of embodiment of the pharmaceutical composition of prevention insulin resistance relevant disease of the invention, the pharmaceutical composition
The raw material for preparing of object includes following components：Cortex Cinnamomi volatile oil 75g, berberine 25g.
2nd, the preparation method of aforementioned pharmaceutical compositions：
(1) Cortex Cinnamomi volatile oil carbon dioxide supercritical extraction method or extraction by steam distillation are taken, obtains Chinese cassia tree volatilization
Oil extract；Beta-cyclodextrin is weighed by the 10% of Cortex Cinnamomi volatile oil weight, is put in container, adds in purified water, boiling water bath heating makes
It is dissolved, and is placed to 25 DEG C, and after constant temperature stirs 15 minutes, Cortex Cinnamomi volatile oil extract is slowly injected into beta-cyclodextrin, is continued permanent
Temperature stirring is taken out after 30 minutes, is cooled to 25 DEG C, and rapid filtration under suction is first used after being rinsed with a small amount of water, then washed with ether, dry,
Up to the inclusion compound of Cortex Cinnamomi volatile oil extract；
(2) coptis is taken to crush, after sieving, alcohol reflux extraction adds in mass concentration and dissolved by heating for 1% acetic acid, then
Until enriching hydrochloric acid to solution muddiness, cooling is placed, that is, has berberine hydrochloride to salt out, gained crystallization is successively with ice water, acetone
Washing, obtains berberine crude product；Add distilled water to berberine crude product, dissolving is boiled in heating, and it is 9.0 to adjust PH with milk of lime, by filtrate
Cooling acidification is placed, that is, has the precipitation of acicular crystal berberine, berberine crystalline solid at 54 DEG C is dried, obtains berberine fine work
(mass concentration 97%)；
(3) inclusion compound of Cortex Cinnamomi volatile oil extract and berberine fine work are merged into mixing, adds in appropriate auxiliary material, obtain
To the pharmaceutical composition.
Embodiment 6
1st, a kind of embodiment of the pharmaceutical composition of prevention insulin resistance relevant disease of the invention, the pharmaceutical composition
The raw material for preparing of object includes following components：Cortex Cinnamomi volatile oil 20g, berberine 80g.
2nd, the preparation method of aforementioned pharmaceutical compositions：
(1) Cortex Cinnamomi volatile oil carbon dioxide supercritical extraction method or extraction by steam distillation are taken, obtains Chinese cassia tree volatilization
Oil extract；Beta-cyclodextrin is weighed by the 12% of Cortex Cinnamomi volatile oil weight, is put in container, adds in purified water, boiling water bath heating makes
It is dissolved, and is placed to 37 DEG C, and constant temperature stirs after twenty minutes, and Cortex Cinnamomi volatile oil extract is slowly injected into beta-cyclodextrin, is continued permanent
Temperature stirring is taken out after 35 minutes, is cooled to 25 DEG C, and rapid filtration under suction is first used after being rinsed with a small amount of water, then washed with ether, dry,
Up to the inclusion compound of Cortex Cinnamomi volatile oil extract；
(2) coptis is taken to crush, after sieving, alcohol reflux extraction adds in mass concentration and dissolved by heating for 1% acetic acid, then
Until enriching hydrochloric acid to solution muddiness, cooling is placed, that is, has berberine hydrochloride to salt out, gained crystallization is successively with ice water, acetone
Washing, obtains berberine crude product；Add distilled water to berberine crude product, dissolving is boiled in heating, and it is 9.1 to adjust PH with milk of lime, by filtrate
Cooling acidification is placed, that is, has the precipitation of acicular crystal berberine, berberine crystalline solid at 55 DEG C is dried, obtains berberine fine work
(mass concentration 98%)；
(3) inclusion compound of Cortex Cinnamomi volatile oil extract and berberine fine work are merged into mixing, adds in appropriate auxiliary material, obtain
To the pharmaceutical composition.
Embodiment 7
1st, a kind of embodiment of the pharmaceutical composition of prevention insulin resistance relevant disease of the invention, the pharmaceutical composition
The raw material for preparing of object includes following components：Cortex Cinnamomi volatile oil 80g, berberine 20g.
2nd, the preparation method of aforementioned pharmaceutical compositions：
(1) Cortex Cinnamomi volatile oil carbon dioxide supercritical extraction method or extraction by steam distillation are taken, obtains Chinese cassia tree volatilization
Oil extract；Beta-cyclodextrin is weighed by the 12% of Cortex Cinnamomi volatile oil weight, is put in container, adds in purified water, boiling water bath heating makes
It is dissolved, and is placed to 37 DEG C, and constant temperature stirs after twenty minutes, and Cortex Cinnamomi volatile oil extract is slowly injected into beta-cyclodextrin, is continued permanent
Temperature stirring is taken out after 35 minutes, is cooled to 25 DEG C, and rapid filtration under suction is first used after being rinsed with a small amount of water, then washed with ether, dry,
Up to the inclusion compound of Cortex Cinnamomi volatile oil extract；
(2) coptis is taken to crush, after sieving, alcohol reflux extraction adds in mass concentration and dissolved by heating for 1% acetic acid, then
Until enriching hydrochloric acid to solution muddiness, cooling is placed, that is, has berberine hydrochloride to salt out, gained crystallization is successively with ice water, acetone
Washing, obtains berberine crude product；Add distilled water to berberine crude product, dissolving is boiled in heating, and it is 9.2 to adjust PH with milk of lime, by filtrate
Cooling acidification is placed, that is, has the precipitation of acicular crystal berberine, berberine crystalline solid at 56 DEG C is dried, obtains berberine fine work
(mass concentration 97%)；
(3) inclusion compound of Cortex Cinnamomi volatile oil extract and berberine fine work are merged into mixing, adds in appropriate auxiliary material, obtain
To the pharmaceutical composition.
Embodiment 8
1st, a kind of embodiment of the pharmaceutical composition of prevention insulin resistance relevant disease of the invention, the pharmaceutical composition
The raw material for preparing of object includes following components：Cortex Cinnamomi volatile oil 10g, berberine 90g.
2.The preparation method of aforementioned pharmaceutical compositions：
(1) Cortex Cinnamomi volatile oil carbon dioxide supercritical extraction method or extraction by steam distillation are taken, obtains Chinese cassia tree volatilization
Oil extract；Beta-cyclodextrin is weighed by the 12% of Cortex Cinnamomi volatile oil weight, is put in container, adds in purified water, boiling water bath heating makes
It is dissolved, and is placed to 37 DEG C, and constant temperature stirs after twenty minutes, and Cortex Cinnamomi volatile oil extract is slowly injected into beta-cyclodextrin, is continued permanent
Temperature stirring is taken out after 35 minutes, is cooled to 25 DEG C, and rapid filtration under suction is first used after being rinsed with a small amount of water, then washed with ether, dry,
Up to the inclusion compound of Cortex Cinnamomi volatile oil extract；
(2) coptis is taken to crush, after sieving, alcohol reflux extraction adds in mass concentration and dissolved by heating for 1% acetic acid, then
Until enriching hydrochloric acid to solution muddiness, cooling to be placed, that is, has berberine hydrochloride to salt out, gained crystallization ice water, acetone wash,
Obtain berberine crude product；Add distilled water to berberine crude product, dissolving is boiled in heating, and it is 9.5 to adjust PH with milk of lime, filtrate is placed cold
But it is acidified, that is, has the precipitation of acicular crystal berberine, berberine crystalline solid at 60 DEG C is dried, obtains berberine fine work (quality
It is a concentration of 96%)；
(3) inclusion compound of Cortex Cinnamomi volatile oil extract and berberine fine work are merged into mixing, adds in appropriate auxiliary material, obtain
To the pharmaceutical composition.
Embodiment 9
1st, a kind of embodiment of the pharmaceutical composition of prevention insulin resistance relevant disease of the invention, the pharmaceutical composition
The raw material for preparing of object includes following components：Cortex Cinnamomi volatile oil 90g, berberine 10g.
2nd, the preparation method of aforementioned pharmaceutical compositions：
(1) Cortex Cinnamomi volatile oil carbon dioxide supercritical extraction method or extraction by steam distillation are taken, obtains Chinese cassia tree volatilization
Oil extract；Beta-cyclodextrin is weighed by the 15% of Cortex Cinnamomi volatile oil weight, is put in container, adds in purified water, boiling water bath heating makes
It is dissolved, and is placed to 50 DEG C, and after constant temperature stirs 30 minutes, Cortex Cinnamomi volatile oil extract is slowly injected into beta-cyclodextrin, is continued permanent
Temperature stirring is taken out after 50 minutes, is cooled to 25 DEG C, and rapid filtration under suction is first used after being rinsed with a small amount of water, then washed with ether, dry,
Up to the inclusion compound of Cortex Cinnamomi volatile oil extract；
(2) coptis is taken to crush, after sieving, alcohol reflux extraction adds in mass concentration and dissolved by heating for 1% acetic acid, then
Until enriching hydrochloric acid to solution muddiness, cooling is placed, that is, has berberine hydrochloride to salt out, gained crystallization is successively with ice water, acetone
Washing, obtains berberine crude product；Berberine crude product is added into distilled water, dissolving is boiled in heating, and it is 9.8 to adjust PH with milk of lime, by filtrate
Cooling acidification is placed, that is, has the precipitation of acicular crystal berberine, berberine crystalline solid at 58 DEG C is dried, obtains berberine fine work
(mass concentration 95%)；
(3) inclusion compound of Cortex Cinnamomi volatile oil extract and berberine fine work are merged into mixing, adds in appropriate auxiliary material, obtain
To the pharmaceutical composition.
The pharmacodynamic experiment of the pharmaceutical composition of 10 present invention of embodiment
To verify pharmacological action of the drug of the present invention in the disease that treatment insulin resistance is pathophysiological basis, face for it
Bed application provides scientific basis, and spy carries out following pharmacodynamic experiment.This experiment uses insulin resistant mice model, detects pancreas islet
The index of correlation that element is resisted.
1.1 zoopery
1.1.1 experimental subjects
C57BL/6J mouse (are provided, credit number by Guangdong Medical Lab Animal Center：SCXK (Guangdong) 2013-
0002), half male and half female, 18~22g.
1.1.2 experiment condition
Cleaning grade animal house, temperature be (22-25 DEG C), relative humidity 40%~60%, the 12/12h light and shade periods, freely into
Food drinking-water.Management of laboratory animal and the pertinent regulations of protection are abided by the raising of animal and materials in experimentation.
1.1.3 major experimental instrument and equipment
Roche Modular-ISE9OO-P800 type automatic clinical chemistry analyzers；Electronic balance BP12lS types；LDZ5-2 platforms
Formula low speed autobalancing centrifuge；Spectrumlab22PC type spectrophotometers；The full-automatic blood cells of Japanese photoelectricity MEK-6318K
Analyzer；Thermo adjustable pipettes；LEICARM2135 slicers；III type biological tissue embedding machines of BMJ-；TSJ-Q types are complete
Automatic closing type tissue processor；Instrument is dried in the drift of III type pathological tissues of PHY-；OLYMPUS-BX40 light microscopes.
1.1.4 tested medicine
Experimental group 1 is the medicament of embodiment 1, and 2 groups of medicaments for embodiment 2,3 groups of medicaments for embodiment 3,4 groups are real
The medicament of example 4 is applied, 5 groups of medicaments for embodiment 5,6 groups of medicaments for embodiment 6,7 groups of medicaments for embodiment 7,8 groups are real
Apply the medicament of example 8,9 groups of medicaments for embodiment 9
1.2 experimental method
1.2.1 the foundation of IR mouse models
According to literature method【3】Insulin resistant mice model is established with the method for feeding high-sugar-fat-diet.Feed is matched
Side (g/100g)：Fructose 60%, fat 15%, protein 21%, fiber 3%, vitamin and mineral 1%.
1.2.3 experiment reagent
Glucose kit is purchased from Guangzhou Sheng Wei bio tech ltd.Insulin ELISA kit is by U.S. R＆D public affairs
Department provides.Rosiglitazone (rosiglitazone, RSG) is Sigma Co., USA's product.
1.2.2 mice group and medication
C57BL/6J mouse are randomly divided into after modeling success：Model group, positive controls (Rosiglitazone 1mg/kg/
D), experimental group 1-9 groups.10 conventional feeds of Normal group are fed.12 groups altogether, every group 10.Gastric infusion, each gavage
Dosage is 150mg/kg/d, one time a day, continues 8W.
During the experiment mouse free water is fed, and food ration is recorded per 1d, and every 3 days record weight continuously feed 14w.End
After secondary feeding, be deprived of food but not water 10h, heart extracting blood is conventional to detach serum, be stored in 4 DEG C it is spare.
1.2.3 observation index
(1) measure of fasting blood glucose level
After last feeding, mouse is deprived of food but not water 5h, and tail vein takes 10 μ L of blood to be added in the protein precipitant of 0.2mL,
7min, 4500r/min are stored at room temperature, centrifuges 15min, takes 150 μ L of supernatant, is measured with reference to glucose kit specification method empty
Abdomen blood glucose level.
(2) measure of oral glucose tolerance
After last feeding, mouse is deprived of food but not water 5h, the glucose solution of gavage 2g/kg, after gavage 0,0.5,1,2h
Tail vein takes 10 μ L of blood to measure the moment blood glucose level respectively, and area (area under glucose curve is calculated according to the following formula
Under the curve, AUC)：
AUC(h·mmol/L-1)=0.25 × A+0.5 × B+0.75 × C+0.5 × D (A, B, C, D represent 0 respectively, 0.5,
1st, the blood glucose level of 2h)
(3) measure of serum insulin level
After last feeding, mouse is deprived of food but not water 10h, plucks eyeball and takes blood, after being stored at room temperature 30min, 7500r/min centrifugations
15min takes 10 μ L of serum, and serum insulin level is measured with reference to ELISA kit specification.It calculates respectively according to the following equation
Model evaluation insulin resistance index (insulin resistance index, HOMA-IR) and insulin sensitivity detection refer to
Number (quantitative insulin sensitivity check index, QUICKI):
HOMA-IR=fasting blood glucose levels × serum insulin level/22.5
QUICKI=1/ (lg fasting blood glucose level+lg serum insulin levels)
(4) mouse weight weightening measures
1.2.4 statistical analysis：
Experimental result is represented with x ± s, carries out single factor test one-way ANOVA variance analyses using SPSS17.0 softwares, together
When compared two-by-two with Tukeys methods, using P ﹤ 0.05 as with the difference on statistical significance.
1.3 result
1.3.1 mouse general status
Normal group mouse expression is quiet, active active, and fur is bright and clean neat, and eyes have god, to food allergy, escapes
Reaction is fast.
Occur weight loss, more drinks, diuresis, few dynamic, apathetic, slow in reacting, hair after model group mouse modeling success
Phenomena such as perpendicular tarnish, slow movement, tail are crispaturaed, and limb tail is clammy, moist around vulva, the curling back of a bow.
Start gavage after medicine group modeling of the present invention and carry out drug therapy, compared with model group, test each group mouse
Behaviouristics performance has certain improvement, wherein experimental group 4 significantly.
1.3.2 the increased weight of mouse
Influence of 1 Chinese medicine composition of table to insulin resistant mice increased weight
Note：#P<0.05, ##P<0.01, compared with Normal group.*P<0.05, * * P<0.01 compared with model group.
Obesity is to lead to the important risk factor of insulin resistance and hyperglycemia.There are insulin to support by 80% obese patient
Anti- or hyperglycemic symptoms, and being proportionate property.Display experiment each group mouse AUC area change situations as shown in Figure 1：With it is normal right
Compare according to group, the food ration of model group and each tested material group mouse is remarkably decreased (P ﹤ 0.05).Model control group mouse weight
Increment is apparently higher than Normal group (P<0.01).Compared with model control group, each group mouse weight of Chinese medicine composition is fed
Increment is remarkably decreased (P ﹤ 0.05)；RSG group mouse weight increments are without significant changes (P ＞ 0.05)；4 mouse weight increment of experimental group
It is remarkably decreased (P ﹤ 0.01).With positive control RSG group ratios, 4 mouse weight increment of experimental group is remarkably decreased (P ﹤ 0.05).As a result table
The bright each experimental group of Chinese medicine composition can significantly inhibit the weight gain of insulin resistant mice, and 4 effect of experimental group is best.
1.3.3 influence of the Chinese herbal compounds to insulin resistant mice index of correlation
The influence (n=10) of 2 Chinese herbal compounds of table each index to insulin resistant mice
Note：##P<0.01 compared with Normal group；*P<0.05, * * P<0.01 compared with model group；★P<0.05 with
RSG groups compare.
As shown in Table 2, model mice fasting blood glucose level is significantly higher than Normal group (P ﹤ 0.01).Chinese medicine composition with
Model control group compares, and Chinese medicine composition each group mouse fasting blood glucose level is remarkably decreased；With experimental group 4 most significantly.With the positive
Control RSG groups compare no significance,statistical.The result shows that test each group of fasting blood syrup that can significantly reduce RI mouse
Flat, 4 effect of experimental group is best.
Insulin is an internal unique hypoglycemic hormone, and glucose metabolism is played an important role.It is supported in insulin
Under anti-state, insulin promote glucose transport uptake and utilization function be damaged, body be maintenance blood glucose normal level and
Compensatory promotes the secretion of insulin, and internal insulin content is caused to rise, and generates hyperinsulinemia, serum insulin content
It is higher, illustrate that insulin resistance degree is more serious.HOMA-IR is the index for evaluating individual insulin resistance degree；
QUICKI is the index for evaluating individual insulin sensitivity.As shown in Table 2, testing each group is reducing insulin water
Flat, mitigation insulin resistance has remarkable result, 4 (Cortex Cinnamomi volatile oil of experimental group in terms of increasing insulin sensitivity：Berberine=
1：3) effect is optimal.
1.3.4 influence of the Chinese herbal compounds to model mice glucose tolerance
Glucose tolerance test is one of standard of diagnosis diabetes generally acknowledged at present, and glucose tolerance is to reflect in short-term
The good index that blood glucose value changes in phase, represents that AUC is bigger with area under glucose curve (AUC), shows individual to glucose
Tolerance it is smaller, occur diabetes probability increase.Shown in Fig. 1, AUC, 4 effect of experimental group can be reduced by testing each group
It is optimal.
In conclusion each group of Chinese herbal compounds can reduce weight gain and the Fat Accumulation of insulin resistant mice,
It reduces blood glucose level and improves insulin resistance (P ＜ 0.05)；Experimental group 4 is reducing insulin compared with other Chinese traditional medicine compositions
Weight gain and the Fat Accumulation of mouse are resisted, optimal (the P ＜ of effect in terms of reducing blood glucose level and improving insulin resistance
0.01), prompting drug is in Cortex Cinnamomi volatile oil：Berberine=1：With best pharmacodynamics effect when 3, there is phase with above-mentioned behaviouristics
Same conclusion.
1.2 cell experiment
1.2.1 experiment material
1.2.1.1 Chinese herbal compounds and cell strain
Before Cortex Cinnamomi volatile oil, the extraction of berberine Chinese herbal compounds are shown in.Allocation ratio Cortex Cinnamomi volatile oil：Berberine=1：3.
3T3-L1 PECTORAL LIMB SKELETONs, purchased from Type Culture Collection companies of the U.S., with DMEM complete mediums
It cultivates, containing 10%NCS, 1 × 10 in base5U/L penicillin and 1 × 105μ g/L streptomycin sulphates.In 37 DEG C, 5%CO2, saturation it is wet
The CO of degree2Routine passage adhere-wall culture in incubator, and with 0.25% pancreatin had digestive transfer culture.
1.2.1.2 experiment reagent
Glucose kit is purchased from Guangzhou Sheng Wei bio tech ltd.Super quick ECL chemical luminescence reagent kits are purchased from north
Capital Puli's lema gene Technology Co., Ltd..30% acrylamide, bovine serum albumin(BSA), Tris-base, glycine, APS, sucrose
It is provided by Beijing Suo Laibao Science and Technology Ltd.s.Contrasting power, fixing powder are purchased from scaphe industrial arts factory of Wenzhou City.Western
And IP lysates are U.S.'s Invitrogen Products.Bovine serum albumin(BSA), 4 × albumen sample solution, TEMED, insulin,
PMSF, TNF-α, trypsase are purchased from Sigma Co., USA.X-ray film is the production of Kodak Company company of the U.S..
Wortmannin, MK2206, U0126 are provided by selleck chemicals companies of the U.S..DMEM(Dulbecco’s
Modified Eagles Medium) culture medium, calf serum be purchased from Gibco companies of the U.S..Other reagents are domestic.
1.2.1.3 key instrument
GL-20M type high speed freezing centrifuges, Shanghai Lu Xiang instrument centrifuges Instrument Ltd.
WGP-300 type constant incubators, Anting Scientific Instrument Factory, Shanghai
EPS600 electrophoresis apparatuses, VE-180 Vertial electrophorestic tanks, Shanghai Tian Neng Science and Technology Ltd.s
PH3-3C type pH meters, Shanghai Sheng Ci Instrument Ltd.
DYCP-40C type transferring films electrophoresis apparatus, WD-9405A type decolorization swinging tables, Liuyi Instruments Plant, Beijing
DL-CJ-1N type superclean benches, Beijing Dong Lianhaer instrument manufacturings Co., Ltd
2711 type CO2Incubator, German Heraeus companies
Mode1680 type microplate reader, Bio-Rad companies of the U.S.
1.2.2 experimental method
1.2.2.1 grouping
Before Cortex Cinnamomi volatile oil, the preparation of berberine Chinese herbal compounds are shown in.Allocation ratio Cortex Cinnamomi volatile oil：Berberine=1：3.
It is grouped into：Ripe 3T3-L1 groups of cells (blank control), insulin resistance group (IR), RSG positive controls (Rogers
Row ketone, final concentration of 3.4mg/L), Chinese medicine group.
1.2.2.2 the induction differentiation of 3T3-L1 PECTORAL LIMB SKELETONs
The 3T3-L1 PECTORAL LIMB SKELETONs in growth period of taking the logarithm are inoculated in (3 × 10 in 24 orifice plates7/ L, DMEM are cultivated completely
Base), per hole 1mL.Continue to cultivate 48h after cell covers with, change IBMX containing 0.5mM, 1 μM of DEX, 10 μ g/mL insulin into
Complete medium culture (differentiation 0d).Change the complete medium (differentiation 2d) containing 10 μ g/mL insulin after 48h into.After
Liquid is changed in differentiation 4d and differentiation 6d respectively, cell is divided into mature fat cell in differentiation 8d.
1.2.2.3 the foundation of 3T3-L1 insulin resistance cell models
Induction is carried out to 3T3-L1 mature fat cells using TNF-α and establishes insulin resistance cell model.Take differentiation
8d mature fat cells add in serum-free, the DMEM culture mediums containing 0.5% (w/v) bovine serum albumin(BSA) and 25mm glucose
Cultivate 12h.Cell is divided into Normal group and TNF-α processing group, TNF-α processing group change into containing 10ng/mL TNF-α,
The DMEM culture mediums of 10% newborn bovine serum and 25mm glucose, Normal group change complete medium into.For 24 hours afterwards with containing
The insulin processing 30min of 100nm collects supernatant, glucose kit detection glucose transport amount, to judge insulin model
Whether it is successfully established.
1.2.2.4 Western blot are analyzed
Chinese herbal compounds are detected to insulin resistant model cell PI3K/PKB signal paths using Western blot methods
Key gene (PI3K, PKB, GLUT4) protein expression and phosphorylation level and ERK protein expressions and phosphorylation level carry out
It measures.The cell collected in above-mentioned experiment is taken, adds in 200 μ L Western and IP lysates, low speed is homogenized or blows and beats in ice bath
Total protein in cell extraction cell, 7 500r/min centrifugation 15min, takes supernatant, BCA kits detect its content.Take 50 μ g
Total protein (epicyte including extraction) adds in appropriate 4 × albumen sample solution, and boiling water bath 10min makes albuminous degeneration, -20 DEG C of guarantors
It deposits spare.
1.2.2.5 statistical analysis
Experimental result withIt represents, single factor test variance one-way ANOVA analyses is carried out using SPSS17.0 softwares, together
When compared two-by-two with Tukey ' s methods, using P ﹤ 0.05 as with the difference on statistical significance.
1.2.3 experimental result
PI3K/PKB Insulin signaling pathways are the main paths of glucose transport, and it is compound that this experiment has detected Chinese medicine
Influence of the object to insulin resistant model cell PI3K protein expressions, Fig. 2 display experiment each group mouse p-p85-PI3K albumen tables
Up to situation of change, as can be seen from Figure 2, compared with blank control group, IR group PI3K total proteins are without significant changes.Compared with IR groups,
P-p85-PI3K protein expressions under Chinese herbal compounds group, Cortex Cinnamomi volatile oil group, berberine group insulin stimulating dramatically increase,
The p85 of PI3K is promoted to adjust the phosphorylation of subunit.Compared with RSG groups, Chinese herbal compounds group further promotes the phosphorus of the p85 of PI3K
It is acidified (P ﹤ 0.05).Show that Chinese herbal compounds group, Cortex Cinnamomi volatile oil group, berberine group can be by activating PI3K to promote model cell
Glucose is transported, all has obvious effect to insulin resistance.Cortex Cinnamomi volatile oil is that mutual reinforcement between acts on berberine, both compounds
Effect it is more excellent than Cortex Cinnamomi volatile oil group, berberine group effect.
2 clinical comparisons are tested
2.1 case selection
Selected case is hospitalized from Guangzhou Nanfang Hospital and outpatient.Meet insulin resistance diagnostic criteria, age
In the patient of 18~70 years old.In difference there are no significant (the P ﹥ of gender, age, Pathogenesis etc. before three groups of Case treatments
0.05), show that balance between the two groups is preferable, be comparable.And meet the following conditions:(1) sanity, can partner treatment；(2)
Without infectious disease mental disease and poisoning disease.According to/exclusion criteria is included in, according to patient's Principles in Informed Consent, by 210
Patient is randomly divided into 7 groups, and each group observes 30.
The diagnostic criteria of 2.2 IR：
HOMA-IR=fasting blood glucose levels × serum insulin level/22.5
HOMA-IR >=2.8 are diagnosed as IR
2.3 therapy
Primary Care：Patient enters the symptomatic treatments such as diet control before group, kinesiatrics, conventional hypoglycemic, lipid-loweringing and decompression, into
The above-mentioned medicine type in this research process of row Central Plains, metering maintain not in principle in addition to the state of an illness changes and need to be adjusted
Become.Each group carries out Primary Care.
2.4 treatment groupings
Blank control group (A)：Maintain Primary Care.
Chinese medicine control group (B)：The patent application of Publication No. CN1364610A disclose it is a kind of treat diabetes it is pure in
Medicine preparation blood-sugar reducing tea is by radix polygonati officinalis, pueraria lobata, Radix Astragali, Chinese yam, pumpkin, balsam pear, soya bean, Chinese gall, green tea, Pogostemon cablin, mulberry Piao
Octopus, garlic, Radix Glycyrrhizae, pollen, berberine, tea bag made of Cortex Cinnamomi volatile oil.Specific preparation method is said for above-mentioned patent application
Method described in bright book inverse 1-5 rows of page 1.Instructions of taking：3 times a day, each 100ml.
Cortex Cinnamomi volatile oil and Berberine in treating group (C)：Granule prepared by following embodiments 1, warm boiled water, daily
2 times, each taking 1 parcel (Cortex Cinnamomi volatile oil containing 0.1g and 0.3g berberines, ratio 1：3).
Independent Cortex Cinnamomi volatile oil treatment group (D)：The inclusion compound of independent Cortex Cinnamomi volatile oil extract, warm boiled water, daily 2
It is secondary, each taking 1 parcel (containing Cortex Cinnamomi volatile oil 0.1g).
Independent Berberine in treating group (E)：Independent coptis extract, warm boiled water, 2 times a day, each taking 1 parcel
(containing berberine 0.3g).
2.5 evaluation index
HOMA-IR, fasting blood-glucose (FPG), fasting insulin (FINS) are horizontal.
FPG is measured：Using glucose oxidase method；FINS is measured：Using radioimmunology.
2.6 statistical method
Using SPSS17.0 softwares, meet the measurement data mean ± standard deviation of normal distributionIt represents, does not meet
The data of normal distribution are converted into approximate normal distribution, then use statistical procedures using natural logrithm.Group difference uses t
It examines；Enumeration data uses Chi-square Test；Correlation between index of correlation uses Liner correlation.
2.6 result
A, two groups of FPG, FINS and HOMA-IR of B are above C, D, E group (P<0.01)；A, FPG, FINS and HOMA- between B groups
IR no significant differences (P>0.05).Prompt general treatment group that there are apparent insulin resistance, Gui Lian with Chinese medicine control group
Each group of insulin resistance of Chinese medicine weakens or disappears.D (inclusion compound of independent Cortex Cinnamomi volatile oil extract), E groups (the independent coptis
Extract) both can improve the situation of insulin resistance, wherein C groups (Cortex Cinnamomi volatile oil：Berberine=1:1) effect is most
It is good.
FPG, FINS, HOMA-IR compare between 3 three groups of table
Note：*P<0.05, * * P<0.01, #P ＞ 0.05, compared with A groups；★P<0.01 compared with B groups
2.7 conclusion
This clinical trial is started with from the insulin resistances index of correlation such as FPG, FINS and HOMA-IR, in addition to having patent
Results of comparison is shown, with the Cortex Cinnamomi volatile oil berberine 1 of dosage：The compound group of 3 proportionings is mitigating insulin resistance
In tri- indexs of FPG, FINS and HOMA-IR, than the independent Cortex Cinnamomi volatile oil extract group of same dosage and with the independent of dosage
Coptis extract group, effect is more preferable, illustrates that Cortex Cinnamomi volatile oil, berberine compatibility play the role of synergistic, reduction dosage.
In conclusion zoopery proves, the grouping of each ratio of Chinese herbal compounds can reduce insulin resistant mice
Weight gain and Fat Accumulation, reducing blood glucose level simultaneously improves insulin resistance (P ＜ 0.05)；Experimental group 1 and other Chinese medicines
Combination is compared, and is reducing the weight gain of insulin resistant mice and Fat Accumulation, is reduced blood glucose level and is improved insulin and supports
Anti- aspect effect is optimal (P ＜ 0.01), prompts drug in Cortex Cinnamomi volatile oil：Berberine=1：With best pharmacodynamics effect when 3,
There is identical conclusion with above-mentioned behaviouristics.Cell experiment proves, Cortex Cinnamomi volatile oil and berberine Chinese herbal compounds group, independent meat
Osmanthus volatile oil group, independent berberine group all can have insulin resistance by activating PI3K that model cell is promoted to transport glucose
Obvious effect.Cortex Cinnamomi volatile oil is mutual reinforcement between effect with berberine, and the effect of both compounds is than Cortex Cinnamomi volatile oil group, berberine
Group effect is more excellent.Clinical trial is started with from the insulin resistances index of correlation such as FPG, FINS and HOMA-IR, compares Cortex Cinnamomi volatile oil
The compound of berberine different proportion, it is 1 to find pharmaceutical composition proportioning：3 have the effect of best.In addition to having patent pair
According to the results show that independent Cortex Cinnamomi volatile oil extract and independent coptis extract, all can independently mitigate insulin resistance, be
Mutual reinforcement between relationship, the two proportioning are 1：3 compound has optimal effectiveness in tri- indexs of FPG, FINS and HOMA-IR.Explanation
Chinese medicine composition of the present invention can have the effect for the treatment of insulin resistance.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than the present invention is protected
The limitation of range is protected, although being explained in detail with reference to preferred embodiment to the present invention, those of ordinary skill in the art should
Understand, technical scheme of the present invention can be modified or replaced equivalently, without departing from the essence of technical solution of the present invention
And range.
Claims (8)
- A kind of 1. pharmaceutical composition for preventing insulin resistance relevant disease, which is characterized in that the preparation of described pharmaceutical composition Raw material includes the component of following mass percentage：Cortex Cinnamomi volatile oil 10~90% and berberine 10~90%.
- 2. pharmaceutical composition according to claim 1, which is characterized in that the raw material for preparing contains comprising following quality percentage The component of amount：Cortex Cinnamomi volatile oil 25% and berberine 75%.
- 3. pharmaceutical composition according to claim 1, which is characterized in that the raw material for preparing contains comprising following quality percentage The component of amount：Cortex Cinnamomi volatile oil 50% and berberine 50%.
- 4. pharmaceutical composition according to claim 1, which is characterized in that the insulin resistance relevant disease for it is fat, Diabetes, hyperlipidemia, metabolic syndrome or hypertension etc..
- 5. pharmaceutical composition according to claim 1, which is characterized in that the Cortex Cinnamomi volatile oil is derived from Lauraceae aiphyllium The dry hide of plant Chinese cassia tree or/and thick branch skin；The berberine is derived from the green radicle among the mature seed of nymphaeaceae plant lotus.
- 6. such as the preparation method of Claims 1 to 5 any one of them pharmaceutical composition, which is characterized in that the preparation method Include the following steps：(1) Chinese cassia tree is taken to extract, obtains Cortex Cinnamomi volatile oil extract；Beta-cyclodextrin and purified water are taken, is heated in boiling water bath To dissolving, treat that temperature is down to 25~50 DEG C, after constant temperature stirs 15~30 minutes, Cortex Cinnamomi volatile oil extract is slowly injected into described In beta-cyclodextrin, continuation constant temperature stirring 30~take out after sixty minutes is cooled to 25 DEG C, and rapid filtration under suction, washing, drying are to get meat The inclusion compound of osmanthus extractive of volatile oil；(2) coptis is taken to crush, after sieving, alcohol reflux extraction adds in the acetic acid that mass concentration is 1% and dissolves by heating, Ran Houjia Until concentrated hydrochloric acid to solution muddiness, cooling is placed, that is, has berberine hydrochloride to salt out, gained crystallization ice water, acetone are successively washed It washs, obtains berberine crude product；Into gained berberine crude product plus distilled water, dissolving is boiled in heating, with milk of lime adjust PH be 8.5~ 9.8, filtrate is placed into cooling acidification, that is, has needle-shaped coptis cellulose crystal to be precipitated, gained coptis cellulose crystal is dried at 50~60 DEG C It is dry, obtain the berberine fine work of more than 95% mass concentration；(3) inclusion compound of the Cortex Cinnamomi volatile oil extract and the berberine fine work are mixed, added in needed for various dosage forms Auxiliary material is up to described pharmaceutical composition.
- 7. preparation method according to claim 6, which is characterized in that the weight of the beta-cyclodextrin is volatilized for the Chinese cassia tree The 10~20% of weight of oil.
- 8. preparation method according to claim 6, which is characterized in that Cortex Cinnamomi volatile oil uses dioxy in the step (1) Change carbon supercritical extraction or extraction by steam distillation, obtain Cortex Cinnamomi volatile oil extract.
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| CN112457423A (en) * | 2020-12-01 | 2021-03-09 | 温州大学 | Natural extracted compound polysaccharide with function of improving insulin resistance and application thereof |
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Application publication date: 20180706 |