CN109260217A - 3`- deoxyinosine nucleosides is in preparation for the application in a variety of disease drugs, food or health care product - Google Patents
3`- deoxyinosine nucleosides is in preparation for the application in a variety of disease drugs, food or health care product Download PDFInfo
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- CN109260217A CN109260217A CN201811157346.7A CN201811157346A CN109260217A CN 109260217 A CN109260217 A CN 109260217A CN 201811157346 A CN201811157346 A CN 201811157346A CN 109260217 A CN109260217 A CN 109260217A
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- deoxyinosine
- nucleosides
- deoxyinosine nucleosides
- food
- drug
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A61P31/10—Antimycotics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
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Abstract
The present invention relates to drug fields, provide application of the 3`- deoxyinosine nucleosides in the food of preparation prevention or treatment Diet-induced obesity disease or hyperlipemia, drug or health care product, application of the 3'- deoxyinosine nucleosides in the food, drug or health care product for preparing preventing hypertension or artery sclerosis is provided, the application that 3'- deoxyinosine nucleosides prepares skin care item is additionally provided.The present invention studies have shown that 3'- deoxyinosine nucleosides have the function of significant hyperlipemia therapeutic effect, reduction Diet-induced obesity disease weight, overcome existing technology prejudice.And 3'- deoxyinosine nucleosides has more fully curative effect relative to existing drug in terms of preventing or treating hyperlipemia.Meanwhile 3'- deoxyinosine nucleosides can be effectively prevented the generation of hypertension, artery sclerosis by reducing lipids in serum content of material and hdl concentration.
Description
Technical field
The present invention relates to technical field of pharmaceuticals, and in particular to 3'- deoxyinosine nucleosides is high in preparation prevention or treatment
Application in blood lipid disease, the food of Diet-induced obesity disease, drug or health care product, 3'- deoxyinosine nucleosides prevent in preparation
Application in the food of hypertension or artery sclerosis, drug or health care product, 3'- deoxyinosine nucleosides is in preparing skin care item
Application.
Background technique
There are about 12,000,000 people to die of cardiovascular and cerebrovascular disease every year in the whole world, and hyperlipidemia is to cause the master of cardiovascular and cerebrovascular disease
One of because, Chinese hyperlipidemia patient up to 1.6 hundred million people.Damage of the hyperlipidemia to body be concealment, gradually, progressive and whole body
Property.Its direct damage is to accelerate systemic atherosclerosis, and then lead to numerous related diseases.And caused by hyperlipidemia
Cerebral apoplexy, coronary heart disease, myocardial infarction, the ratio of cardiac sudden death also increase year by year.Currently used fat-reducing medicament is to reduce gallbladder
Based on sterol and triglycerides, including reductase inhibitor, Statins, fibrates and niacin class etc., but these drugs are in clinic
The more serious side effect of such as hepatic injury, palpitaition, rhabdomyolysis can be generated during medication.The hyperlipemic patients of China
Other than a small number of Chinese medicines, import or imitated drug are still used.
The pathogenic factors of hyperlipidemia is more, and pathogenesis is complicated, is related to the abnormal pathologic of multisystem, single position
Drug is generally difficult to obtain satisfied therapeutic effect.In addition, hyperlipemia can cause carbohydrate metabolism disturbance and lead to blood glucose rise, from
And cause a variety of diseases such as diabetes, chronic pancreas impaired organ, therefore, reality in need it is a kind of for hyperlipidemia more preferably
Healing potion and therapeutic scheme.
Summary of the invention
The present invention provides 3'- to solve the problems, such as hyperlipemia therapeutic agent therapeutic effect deficiency in the prior art
Application of the deoxyinosine nucleosides in the food of preparation prevention or treatment hyperlipemia, drug or health care product.
The object of the invention is also to provide the application of 3'- deoxyinosine nucleosides in other respects.
To solve the above-mentioned problems, the present invention provides following technical schemes:
The present invention provides 3'- deoxyinosine nucleosides preparation prevention or the treatment food of hyperlipemia, drug or
Application in health care product.
The present invention also provides 3'- deoxyinosine nucleosides preparation prevention or treatment Diet-induced obesity disease food,
Application in drug or health care product,
The present invention also provides 3'- deoxyinosine nucleosides in the food, drug or health care product for preparing preventing hypertension
In application.
The present invention also provides 3'- deoxyinosine nucleosides in food, drug or the health care for preparing prevention of arterial hardening
Application in product.
The present invention also provides 3'- deoxyinosine nucleosides to prepare the application in skin care item.
Preferably, the 3'- deoxyinosine nucleosides preparation method the following steps are included:
It is mixed after being dissolved 3'-Deoxyadenosine with water with adenosine deaminase, 0.8~2h is reacted at 37 DEG C, weight after concentration
Crystallization, gained crystallization are 3'- deoxyinosine nucleosides.
Preferably, the mass ratio of the 3'-Deoxyadenosine and adenosine deaminase is 800~1200:1.
Preferably, the step of being recrystallized after the concentration are as follows:
Solution after reaction has been concentrated into crystallization to be precipitated, reheating dissolves crystallization, stand at 3~6 DEG C 10~16h into
Row recrystallization, separation crystallize up to 3'- deoxyinosine nucleosides.
Preferably, described 35~40 DEG C of heating temperature that dissolve crystallization.
Preferably, in the food, drug or health care product 3'- deoxyinosine nucleosides mass fraction 0.01%~
99.99%.
Compared with prior art, technical solution provided by the invention has the advantage that
The present invention is research shows that 3'- deoxyinosine nucleosides has significant adjusting blood fat function, using 3'- deoxidation time
Xanthosine treats combined hyperlipidemia familial rat model, the results show that 3'- deoxyinosine nucleosides can have
Effect reduces TC (triglycerides) index, TG (total cholesterol) index, LDL (low density lipoprotein cholesterol) water of rat model
It is flat, additionally it is possible to which that significantly raising HDL (high-density lipoprotein cholesterol) is horizontal, that is, it is aobvious to show that 3'- deoxyinosine nucleosides has
The hyperlipemia of work is prevented or therapeutic effect.Meanwhile present invention research is it is also shown that 3'- deoxyinosine nucleosides and conventional height
Blood lipid disease therapeutic agent fenofibrate, simvastatin refer to when reducing mix type hyperlipidemia rat model reducing TC and TG
Pharmacological action is also equipped with more significant without significant difference relative to both conventional medicines 3'- deoxyinosine nucleosides when mark
Reduction rat model serum LDL levels effect, have raising serum hdl water not available for fenofibrate and Simvastatin
Flat effect, thus 3'- deoxyinosine nucleosides provided by the invention be prepared as prevent or treat hyperlipemia food,
There is more preferably pharmacological activity than existing drug after drug or health care product.
3'-Deoxyadenosine also known as Cordyceps militaris element, cordycepin, are the nucleic acid derivative of nitrogenous glycocide.Cordycepin conduct
One of nucleosides active component of cordyceps sinensis Chinese medicine has significant pharmacological action.It is existing research shows that (Chinese patent
CN107737136A), the composition of 3'-Deoxyadenosine and berberine hydrochloride can effectively adjust blood lipid and weight.This is existing
Technology also discloses the analogue that can choose 3'-Deoxyadenosine and berberine hydrochloride forms composition.
3'- deoxyinosine nucleosides can be made of 3'-Deoxyadenosine deamination, however some research tables of this field
Bright, the effect of adenosine deaminase is so that 3'-Deoxyadenosine is converted into 3'- deoxyinosine to lose the drug effect (nine divisions of China in remote antiquity Luo Shanshan worm
The separation of primary medicinal component and biological activity research [D] Shandong University in grass, 2006.).The present invention has broken this field
Existing technology prejudice, it is hard about hyperlipidemia, Diet-induced obesity, hypertension and artery for 3'- deoxyinosine nucleosides
The effect of the illnesss such as change is studied, and finds that 3'- deoxyinosine nucleosides has significant treatment or prevention hyperlipidemia
The effect of disease and Diet-induced obesity.Also there are good effects simultaneously for preventing hypertension, artery sclerosis.Thus by 3'- deoxidation
Inosine is applied to prepare such drug.
The present invention is studies have shown that treat Diet-induced obesity rat model using 3'- deoxyinosine nucleosides, energy
The weight for enough significantly reducing Diet-induced obesity rat model has significant difference, i.e. 3'- deoxyinosine with rat model
Nucleosides has good therapeutic effect for Diet-induced obesity disease, effectively reduces weight.
The present invention also provides 3'- deoxyinosine nucleosides in the application being prepared as in skin care item, described de- comprising 3'-
The skin care item of oxygen inosine have the function for improving metabolic, anti-aging, weight-reducing, strengthen immunity and antibacterial etc.
Effect.
The embodiment of the present invention is shown, through pig ear skin cutaneous penetration, 3'- deoxyinosine nucleosides is after 5min is administered
It can be detected in diffusion cell, show that 3'- deoxyinosine nucleosides of the present invention is applied to pass through after preparing skin care item
The mode of Transdermal absorption enters body, plays the effects of improving metabolic, anti-aging, weight-reducing, strengthen immunity and antibacterial.
In currently preferred technical solution, the present invention provides a kind of biological synthesis process to prepare high-purity 3'- deoxidation
The method of inosine can obtain the 3'- deoxyinosine nucleosides of 98% or more purity.
Specific embodiment
The present invention provides 3'- deoxyinosine nucleosides preparation prevention or the treatment food of hyperlipemia, drug or
Application in health care product.
In the present invention, the structural formula of the 3' deoxyinosine nucleosides is as shown in formula I:
The research of the invention finds that being controlled using 3'- deoxyinosine nucleosides combined hyperlipidemia familial rat model
It treats, the results show that 3'- deoxyinosine nucleosides can be effectively reduced TC (triglycerides) index of rat model, TG (total gallbladder
Sterol) index, LDL (low density lipoprotein cholesterol) level, additionally it is possible to significantly raising HDL (high-density lipoprotein cholesterol) water
It is flat, that is, show that 3'- deoxyinosine nucleosides has the prevention of significant hyperlipemia or therapeutic effect.
Meanwhile present invention research is it is also shown that 3'- deoxyinosine nucleosides and conventional hyperlipemia therapeutic agent fenofibrate
For special, simvastatin when reducing mix type hyperlipidemia rat model, when reducing TC and TG index, pharmacological action is without significance difference
It is different, significantly more reduction rat model serum LDL is also equipped with relative to both conventional medicines 3'- deoxyinosine nucleosides
Horizontal effect has the effect that serum HDL levels are increased not available for fenofibrate and Simvastatin, so that the present invention mentions
The 3'- deoxyinosine nucleosides of confession is after the food, drug or health care product for being prepared as preventing or treating hyperlipemia than existing
Drug has more preferably pharmacological activity.
The research of the invention finds that being controlled using 3'- deoxyinosine nucleosides combined hyperlipidemia familial rat model
It treats, the results show that 3'- deoxyinosine nucleosides can be effectively reduced TC (triglycerides) index of rat model, TG (total gallbladder
Sterol) index, LDL (low density lipoprotein cholesterol) level, additionally it is possible to significantly raising HDL (high-density lipoprotein cholesterol) water
It is flat, that is, show that 3'- deoxyinosine nucleosides has the prevention of significant hyperlipemia or therapeutic effect.
Meanwhile present invention research is it is also shown that 3'- deoxyinosine nucleosides and conventional hyperlipemia therapeutic agent fenofibrate
For special, simvastatin when reducing mix type hyperlipidemia rat model, when reducing TC and TG index, pharmacological action is without significance difference
It is different, significantly more reduction rat model serum LDL is also equipped with relative to both conventional medicines 3'- deoxyinosine nucleosides
Horizontal effect has the effect that serum HDL levels are increased not available for fenofibrate and Simvastatin, so that the present invention mentions
The 3'- deoxyinosine nucleosides of confession is after the food, drug or health care product for being prepared as preventing or treating hyperlipemia than existing
Drug has more preferably pharmacological activity.
In the present invention, the 3'- deoxyinosine nucleosides can be used as prevention or treat food, the medicine of hyperlipemia
Sole active agent in product or health care product can also compound with other active materials and play prevention or treatment function for composition
Effect.
Hyperlipemia of the present invention includes In Patients With Primary Hyperlipoidemia and secondary hyperlipemia.
Currently preferred, the 3'- deoxyinosine nucleosides plays prevention or treats the effective of hyperlipemia effect
Dosage is preferably 6mg/kg/d~100mg/kg/d, more preferably 50mg/kg/d.
The present invention also provides 3'- deoxyinosine nucleosides preparation prevention or treatment Diet-induced obesity disease food,
Application in drug or health care product.
The present invention is studies have shown that treat Diet-induced obesity rat model using 3'- deoxyinosine nucleosides, energy
The weight for enough significantly reducing Diet-induced obesity rat model has significant difference, i.e. 3'- deoxyinosine with rat model
Nucleosides has good therapeutic effect for Diet-induced obesity disease, effectively reduces weight.
In the present invention, the 3'- deoxyinosine nucleosides can be used as prevention or treat the food of Diet-induced obesity disease
Sole active agent in product, drug or health care product can also compound with other substances and play prevention or treatment function for composition
Effect.
Currently preferred, the 3'- deoxyinosine nucleosides plays prevention or treats Diet-induced obesity disease effect
Effective dose is preferably 6mg/kg/d~100mg/kg/d, more preferably 50mg/kg/d.
The present invention also provides 3'- deoxyinosine nucleosides in the food, drug or health care product for preparing preventing hypertension
In application.
The peripheral resistance of blood vessel, arterial wall elasticity and blood viscosity etc. be an important factor for forming hypertension, and these
Factor is closely related with hyperlipemia.It can be effectively reduced serum TC, TG, LDL using 3'- deoxyinosine nucleosides and improve
The effect of HDL level can effectively control the variation of peripheral vascular resistance, arterial wall elasticity and blood viscosity, to reach
The effect of preventing hypertension.
In the present invention, the 3'- deoxyinosine nucleosides can be used as the food, drug or health care of preventing hypertension
Sole active agent in product can also compound with other substances and play prevention effect for composition.
Currently preferred, the effective dose that the 3'- deoxyinosine nucleosides plays preventing hypertension effect is preferred
For 6mg/kg/d~100mg/kg/d, more preferably 50mg/kg/d.
The present invention also provides 3'- deoxyinosine nucleosides in food, drug or the health care for preparing prevention of arterial hardening
Application in product.
Hyperlipemia will cause disorders of lipid metabolism, and blood viscosity increases, and lipid material is deposited in vascular wall inner membrance, by
Small patch is gradually formed, referred to as athero- artery sclerosis.The present invention can be effectively reduced serum using 3'- deoxyinosine nucleosides
TC, TG, LDL and the effect for improving HDL level prevent patch from being formed so that lipid material deposition be effectively relieved, and realize that prevention is dynamic
The purpose of arteries and veins hardening.
In the present invention, the 3'- deoxyinosine nucleosides can be used as food, drug or the guarantor of prevention of arterial hardening
Sole active agent in strong product, can also compound with other drugs and play prevention effect for composition.
In the present invention, the effective dose that the 3'- deoxyinosine nucleosides plays when prevention of arterial hardens effect is excellent
It is selected as 6mg/kg/d~100mg/kg/d, more preferably 50mg/kg/d.
The present invention also provides 3'- deoxyinosine nucleosides in the application being prepared as in skin care item.
The present invention studies have shown that 3'- deoxyinosine nucleosides as when effective component, effective dose is in skin care item
0.5-2%, more preferably 0.8-1.2%.
In the present invention, the 3'- deoxyinosine nucleosides is prepared by way of can synthesizing extraction or in vitro
It arrives.
In order to obtain the higher 3'- deoxyinosine nucleosides of purity, the present invention is prepared using external biological synthesis process
3'- deoxyinosine nucleosides.
In the present invention, the biological synthesis process of the 3'- deoxyinosine nucleosides it is preferred the following steps are included:
It is mixed after being dissolved 3'-Deoxyadenosine with water with adenosine deaminase, 0.8~2h is reacted at 37 DEG C, weight after concentration
Crystallization, gained crystallization are 3'- deoxyinosine nucleosides.
The present invention can be sloughed the property of amino using 3'-Deoxyadenosine by adenosine deaminase, warm in analogue body in vitro
Degree carries out enzymatic reaction, and time of enzymatic reacting is short, high-efficient, can largely synthesize 3'- deoxyinosine nucleosides.
3'-Deoxyadenosine dissolution is to come into full contact with itself and adenosine deaminase under liquid environment with water by the present invention
And react, water is only used as solvent.It is currently preferred to be carried out according to 30~50g:1L of mass volume ratio of 3'-Deoxyadenosine and water
Dissolution, more preferably 40g:1L.
The present invention mixes the solution after dissolving 3'-Deoxyadenosine with adenosine deaminase, in the present invention, the 3'- deoxidation
The mass ratio of adenosine and adenosine deaminase is preferably 800~1200:1, more preferably 1000:1.
In the present invention, the adenosine deaminase is preferably the raw material of 150~200U/mg of enzyme activity；The 3'-Deoxyadenosine
Preferably raw material of the purity greater than 98% (HPLC).Source Wu Te of the present invention to the 3'-Deoxyadenosine and adenosine deaminase
It is different to limit, using the commercial goods for meeting above-mentioned condition.
The mixture of 3'-Deoxyadenosine and adenosine deaminase is placed in 0.8~2h of reaction at 35~40 DEG C by the present invention, is made
3'-Deoxyadenosine is converted into 3'- deoxyinosine nucleosides by adenosine deaminase catalysis deamination.It is currently preferred, it is described anti-
Answering temperature is preferably 37~38 DEG C；Currently preferred, the reaction time is preferably 1~1.2h.It is currently preferred to pass through
The mode maintaining reaction temperature of heating water bath.
After the reaction was completed, reaction solution is concentrated the present invention, when being concentrated into the precipitation of a small amount of crystal, then is heated
Dissolution is recrystallized when the crystal redissolution of precipitation is placed at 3~6 DEG C, and the crystal that recrystallization is collected after 10~16h is
3'- deoxyinosine nucleosides.
The present invention is not particularly limited the condensing mode, and preferably reduced vacuum is concentrated.It is concentrated when using reduced vacuum
When mode carries out, the pressure of the reduced vacuum concentration is 0.05~0.09MPa, more preferably 0.07MPa；The reduced vacuum
The temperature of concentration is 30~50 DEG C, more preferably 40 DEG C
In the present invention, the temperature heated again is preferably 40~50 DEG C, and more preferably 45 DEG C.When the crystal of precipitation
It can stop heating when disappearance.
In the present invention, the temperature when recrystallization is preferably 4 DEG C.In the present invention, when the standing of the recrystallization
Between preferably 12h so that 3'- deoxyinosine nucleosides is adequately precipitated from solution.
The present invention purifies the 3'- deoxyinosine nucleosides of synthesis in the way of recrystallization, to obtain
Purity is the 3'- deoxyinosine nucleosides that HPLC grades and purity are not less than 98%.
The form of food of the present invention includes but is not limited to cake, beverage, brewed powder and dilated food.
The dosage form of drug of the present invention includes but is not limited to granule, tablet, powder, capsule, oral solution, injection
Agent, spray, aerosol, powder spray, lotion, liniment, paste, emulsion, patch, eye drops, nasal drop, suppository, pill, microballoon
Preparation and tincture.
The dosage form of drug of the present invention can also be sustained release preparation, controlled release preparation or targeting preparation.
The form of health care product of the present invention includes but is not limited to granule, tablet, powder, capsule, oral solution, injection
Agent, spray, aerosol, powder spray, lotion, liniment, paste, emulsion, patch, eye drops, nasal drop, suppository, pill, microballoon
Preparation and tincture.
The form of skin care item of the present invention includes but is not limited to Essence, lotion, cream, facial mask, toner and condensation.
The present invention is according to the forms of the food of preparation, drug, health care product or skin care item and requires different selections suitable
Auxiliary agent, auxiliary material.
In the present invention, in the food, drug, health care product or skin care item, 3'- deoxyinosine nucleosides content exists
0.01%~99.99% (mass percent), more preferably 0.1~45.00%.
In order to further illustrate the present invention, technical solution provided by the invention is retouched in detail below with reference to embodiment
It states, but they cannot be interpreted as limiting the scope of the present invention.
Embodiment 1
The synthesis of 3'- deoxyinosine nucleosides:
It weighs the 3'-Deoxyadenosine of 20.0g, the dissolution of 500mL pure water is added, add 20.0mg adenosine deaminase, 37 DEG C
Heating water bath 1h, reduced vacuum has been concentrated into a small amount of crystal and has been precipitated under conditions of 0.07MPa, 40 DEG C, then 37 DEG C of heating for dissolving,
4 DEG C of standing 12h are recrystallized, and are obtained 3'- deoxyinosine nucleosides (HPLC >=98%)
Embodiment 2
The effect that this test prevents 3'- deoxyinosine nucleosides or treat hyperlipemia is verified.
1, prepared by model
SD rat 20, male, cleaning grade, 180~200g of weight, by Academy of Military Medicine, PLA's reality
Animal center is tested, experimental animal uses credit number: SCXK2015-0001.Rat daily ration-type standard feed (LAD0020, Nantong
Te Luofei), 60% high lipid food of rat (combined hyperlipidemia familial model feed, Nantong Te Luofei).
After a week by rat adaptable fed, it weighs, 20 experimental animals is randomly divided into 2 groups, every group 10, blank pair
Daily ration is given according to group, model group gives high lipid food, after continuous feeding 4 weeks, after fasting 12h, weighs, breaks after last dose 1h
Tail takes blood.
Serum is collected after blood room temperature 2h, 3000r/min centrifugation 30min, for detecting TC, TG, LDL, HDL tetra-
Blood lipids index, and after rat anesthesia is put to death, take intraperitoneal white adipose to weigh.As the result is shown compared with blank group, model
Group rat body weight, TC, TG, LDL are significantly increased, and HDL is significantly reduced, modeling achievement.
2, sample detection
40 mix type hyperlipidemia rat models are prepared according to above-mentioned model preparation method.The animal pattern that will be prepared
It is divided into 4 groups, every group 10, respectively blank group, administration group, positive drug fenofibrate group, positive drug Simvastatin group.Its
Middle blank group feeds high lipid food, and administration group feeds high lipid food and the 3'- deoxyinosine nucleosides of 50mg/kg/d, positive
Drug fenofibrate group feeds high lipid food and fenofibrate, positive drug Simvastatin group feeding high lipid food and pungent cuts down him
Spit of fland.
It after each group continuously feeds 4 weeks, after fasting 12h, weighs after last dose 1h, docking takes blood, blood room temperature
Serum is collected after 2h, 3000r/min centrifugation 30min, for detecting tetra- blood lipids index of TC, TG, LDL, HDL.
3, result
3'- deoxyinosine nucleosides, fenofibrate and Simvastatin can significantly reduce TC index, and group difference is not
Greatly；3'- deoxyinosine nucleosides, fenofibrate, Simvastatin can reduce TG index, and group difference is little；3'- deoxidation time
Xanthosine can significantly reduce LDL level, other two groups of administration groups and model group no significant difference；3'- deoxyinosine
Nucleosides can significant raising HDL levels, other two groups of administration groups and model group no significant difference.
4, conclusion
3 '-deoxyinosine nucleosides reduce hyperlipidemia index TC, TG level on, with positive drug fenofibrate,
Simvastatin effect is suitable；3 '-deoxyinosine nucleosides can reduce LDL level, better than positive drug fenofibrate, pungent cut down him
Spit of fland；In addition, the 3 '-significant raising HDL levels of deoxyinosine nucleosides energy, and fenofibrate, Simvastatin not yet find the work
With.
Embodiment 3
The effect that this test prevents 3 '-deoxyinosine nucleosides or treat Diet-induced obesity disease is verified.
1, animal subject and feed
SD rat 30, male, cleaning grade, 180~200g of weight, by Academy of Military Medicine, PLA's reality
Animal center is tested, experimental animal uses credit number: SCXK2015-0001.Rat daily ration-type standard feed (LAD0020, Nantong
Te Luofei), 60% high lipid food of rat (Research diets D12492,60%cal, the U.S., Research Diets).
2, Diet-induced obesity disease rat modeling
After a week by rat adaptable fed, it weighs, 20 experimental animals is randomly divided into 2 groups, every group 10, blank pair
Daily ration is given according to group, model group gives high lipid food, after continuous feeding 4 weeks, after fasting 12h, weighs, breaks after last dose 1h
Tail takes blood, serum is collected after blood room temperature 2h, 3000r/min centrifugation 30min, for detecting TC, TG, LDL, HDL tetra-
Blood lipids index, and after rat anesthesia is put to death, take intraperitoneal white adipose to weigh.As the result is shown compared with blank group, model
Group rat body weight, TC, TG, LDL are significantly increased, and HDL is significantly reduced, and model achievement.
3, sample detection
40 Diet-induced obesity disease rat models are prepared according to above-mentioned modeling method.The animal pattern being prepared is divided into
4 groups, every group 10, respectively blank group, the high, medium and low dosage group of administration.Wherein blank group feeding high lipid food, administration group height,
In, the 3 '-deoxidations time of 85.5mg/kg/d, 50mg/kg/d, 12.5mg/kg/d are fed outside low dose group feeding high lipid food respectively
Xanthosine.After continuous feeding 30 days, after fasting 12h, weigh after last dose 1h, taken after execution abdomen white adipose,
It hepatectomizes.
4, result
As shown in table 1,3 '-deoxyinosine nucleosides can be substantially reduced food-borne rat body weight, have compared with blank group
There is significant difference, wherein middle dose group is the most obvious.
The rat body weight situation of change of 1 different disposal of table
| Group | Before administration/g | Before administration/g |
| Blank group | 175.2±9.18 | 438.6±13.11 |
| Model group | 177.9±7.26 | 468.1±24.33 |
| Administration group (low dosage) | 172.3±6.12 | 439.8±10.09 |
| Administration group (middle dosage) | 174.6±5.37 | 433.2±15.01 |
| Administration group (high dose) | 173.9±6.04 | 434.7±12.67 |
4 3'- deoxyinosine nucleosides tablet of embodiment
3'- deoxyinosine nucleosides 4g is taken to mix with 96g magnesium stearate, wet granulation is dry, obtains 4g/ after tabletting
The oral tablet of piece.It is prepared into the oral tablet of the nucleosides piece 0.03-4g/ piece of deoxyinosine containing 3'-
5 3'- deoxyinosine nucleosides facial mask of embodiment
With water, glycerol 5~15%, mannitol 0.2~1.0%, polyglutamic acid sodium 0.3~0.5%, beta glucan 0.2
~0.5%, Sodium Hyaluronate 0.02~0.12%, 3'- deoxyinosine nucleosides 0.3~5% and yeast extract 0.5~
1.5%, to impregnate non-woven fabrics after raw material mixing, is prepared into 3'- deoxyinosine nucleosides facial mask.
6 3'- deoxyinosine nucleosides edible powder of embodiment
3'- deoxyinosine nucleosides (1-4%) is added in cornstarch as raw-food material, it is de- to be prepared into 3'-
Oxygen inosine edible powder.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (10)
- Application of the 1.3'- deoxyinosine nucleosides in the food of preparation prevention or treatment hyperlipemia, drug or health care product.
- 2.3'- deoxyinosine nucleosides is in the food of preparation prevention or treatment Diet-induced obesity disease, drug or health care product Using.
- Application of the 3.3'- deoxyinosine nucleosides in the food, drug or health care product for preparing preventing hypertension.
- Application of the 4.3'- deoxyinosine nucleosides in the food, drug or health care product for preparing prevention of arterial hardening.
- 5.3'- deoxyinosine nucleosides is preparing the application in skin care item.
- 6. application described in any one according to claim 1~5, which is characterized in that the 3'- deoxyinosine nucleosides Preparation method the following steps are included:It is mixed after being dissolved 3'-Deoxyadenosine with water with adenosine deaminase, 0.8~2h is reacted at 37 DEG C, is recrystallized after concentration, Gained crystallization is 3'- deoxyinosine nucleosides.
- 7. application according to claim 6, which is characterized in that the mass ratio of the 3'-Deoxyadenosine and adenosine deaminase For 800~1200:1.
- 8. application according to claim 6, which is characterized in that the step of being recrystallized after the concentration are as follows:Solution after reaction is concentrated into crystallization to be precipitated, reheating dissolves crystallization, and 10~16h is stood at 3~6 DEG C and carries out weight Crystallization, separation crystallize up to 3'- deoxyinosine nucleosides.
- 9. application according to claim 8, which is characterized in that described 35~40 DEG C of heating temperature that dissolve crystallization.
- 10. application described in any one according to claim 1~5, which is characterized in that in the food, drug or health care product The mass fraction 0.01%~99.99% of 3'- deoxyinosine nucleosides.
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| CN201811157346.7A CN109260217A (en) | 2018-09-30 | 2018-09-30 | 3`- deoxyinosine nucleosides is in preparation for the application in a variety of disease drugs, food or health care product |
| PCT/CN2019/103929 WO2020063262A1 (en) | 2018-09-30 | 2019-09-02 | Application of 3'-deoxyinosine in preparation of drug, food or health product for multiple disease |
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| WO2020063262A1 (en) * | 2018-09-30 | 2020-04-02 | Shenzhen Sunny Bio-Technology.Co., Ltd | Application of 3'-deoxyinosine in preparation of drug, food or health product for multiple disease |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0738475A1 (en) * | 1995-04-20 | 1996-10-23 | The Hokuren Federation Of Agricultural Cooperatives | Alpha-glucosidase inhibitor, composition principally comprising sugar and containing the same, sweetener, food and feed |
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| CN1330513A (en) * | 1999-04-06 | 2002-01-09 | 东卡罗来纳大学 | Low adenosine anti-sense ligonucleotide, compositions, kit and method for treatment of airway disorders associate with bronchoconstriction, lung infflammations, allergy(ies) and surfactant deplection |
| CN109260217A (en) * | 2018-09-30 | 2019-01-25 | 深圳松乐生物科技有限公司 | 3`- deoxyinosine nucleosides is in preparation for the application in a variety of disease drugs, food or health care product |
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2018
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0738475A1 (en) * | 1995-04-20 | 1996-10-23 | The Hokuren Federation Of Agricultural Cooperatives | Alpha-glucosidase inhibitor, composition principally comprising sugar and containing the same, sweetener, food and feed |
Non-Patent Citations (3)
| Title |
|---|
| 田洋: "黄秋葵的研究进展", 《农业科技与装备》 * |
| 裴文菡等: "药食同用植物黄秋葵的研究进展及开发前景", 《中国医药科学》 * |
| 贾陆等: "黄秋葵水溶性部位化学成分研究", 《中草药》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020063262A1 (en) * | 2018-09-30 | 2020-04-02 | Shenzhen Sunny Bio-Technology.Co., Ltd | Application of 3'-deoxyinosine in preparation of drug, food or health product for multiple disease |
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