CN102973588A - Application of carrageenan in preparing medicament for treating diabetes mellitus - Google Patents

Abstract

The invention discloses novel application of carrageenan in preparing a medicament for treating diabetes mellitus. The medicament can protect a body from insulin resistance due to chronic inflammation caused by activated macrophage generated by fat and other reasons, so that attack or symptom worsening of diabetes mellitus can be inhibited. Carrageenan has good curative effect in a high glucose and lysophosphatidylcholine induced animal model; and the medicaments used in the application can be easily acquired, low in price and stable in properties, are convenient to store and transport, and have wide application prospect.

Description

The application of carrageenan in preparation treatment diabetes medicament

Technical field

The invention belongs to the biological medicine technology field, be specifically related to the application of carrageenan in the medicine of preparation treatment diabetes.

Background technology

Diabetes are the diseases that have a strong impact on people's life health.In recent years along with people life style, the variation of dietary habit, the onset diabetes rate has continuous rising, and age of onset has the trend of continuous rejuvenation.Diabetes are divided into insulin-dependent (I type) and non-insulin-depending type (II type) two large classes generally, in the diabetics, are the type ii diabetes patient more than 90%.

Carrageenan Carrageen, claim again antler glue, carrageenin, Irish Herba corydalis edulis glue, be a kind of general designation of the polysaccharide that extracts from marine red alga (comprising Chondrus, Eucheuma, China fir Trentepohlia and husky Lepidium etc.), it is by galactose and 3 sulfate or the non-sulfuric acid base, and the 6-Anhydrogalactose. is by α-1,3 glycosidic bonds and β-1,4 keys alternately are formed by connecting, and are upper with 1 sulfate at 1, the 3 D galactose unit C4 that connects, molecular weight is more than 200,000, and the structure monomer is as follows:

Carrageenan is white or faint yellow film or fibrous material; Most of alkali metal salts, alkali salt and ammonium salt etc. can improve its gelling ability; It and proteins react generate coordination compound; Degrade with the acid effect.Carrageenan odorless, tasteless, large-scale molecule (molecular weight is more than 100,000 dalton) mutually are crimped onto and form together double-spiral structure.Carrageenan has hydrophilic, viscosity, stability, is used as coagulant, thickening agent, emulsifying agent, and suspending agent, clarifier, stabilizing agent and water binding agent are widely used at food and other industry.

Nearest basic research proves, follow the fat lipid peroxidation that waits physiologic factor to produce to cause for a long time, low-level chronic inflammatory disease, the activated macrophage that wherein is distributed in the fatty tissue can cause significant insulin resistant by some inflammatory factor of long-term expression, make body to insulin insensitivity, then cause diabetic symptom.Therefore for this pathogenesis, can develop targetedly treatment means and medicine.

 

Summary of the invention

The object of the present invention is to provide the application of a kind of carrageenan in preparation treatment diabetes medicament, experiment of the present invention shows that carrageenan has the character of strong inhibition macrophage activation, suppress the expression of relevant inflammatory factors, thereby can alleviate the insulin resistant in the type ii diabetes pathogenic process, alleviate diabetic symptom.Therefore, carrageenan can develop into a kind of medicine for the treatment of type ii diabetes on the principle.

The application of carrageenan of the present invention in preparation treatment diabetes medicament, wherein, described carrageenan molecule amount is 7.2 KD ~ 120 KD.

Use commercial available carrageenan raw material to obtain carrageenan than small-molecular weight by acid hydrolysis (or acid degradation) commonly used, may be to obtain the most easily method of this micromolecular compound, the present invention can obtain by the commercially available carrageenan raw material of hydrochloric acid hydrolysis the carrageenan of different molecular weight size, as with commercially available carrageenan (available from Sigma company, molecular weight 500kD) being dissolved in pH by 20% volume ratio is 1.0 hydrochloric acid solution, in 70 degrees centigrade of water-baths, can obtain the carrageenan of 120kD after 30 minutes, can obtain the carrageenan of 70 kD after 2 hours, obtain the carrageenan of 40 kD after 4 hours, obtain the carrageenan of 13 kD after 6 hours, obtain the carrageenan of 7.2 kD after 10 hours, for subsequent use through the dialysis lyophilizing, the molecular weight of the carrageenan after the degraded detects by gel chromatography and obtains.But, it is the reason that is easier to dissolving or animal body absorptions for the carrageenan larger molecular weight of small-molecular weight that the present invention adopts the carrageenan of the small-molecular weight that obtains after the acid degradation to carry out verification experimental verification, is not to illustrate that the carrageenan of macromolecule does not have the function for the treatment of diabetes of the present invention.

Adopt carrageenan of the present invention, combine with multiple pharmaceutically acceptable carrier, by such as oral cavity, vein, nasal cavity, rectum or other any administering modes that can carry the active substance of effective dose, can be prepared into various liquid preparations such as injection, oral liquid formulations etc., also can be prepared into various effectively and be easy to solid preparation such as capsule, the suppository etc. of administration.Wherein, be used for injection or liquid preparation for oral use, its required carrier can be the medically acceptable carriers such as sterilized water, Sterile Saline or water solublity organic carrier such as cyclodextrin, Semen Maydis oil, olive oil, ethyl oleate, glycols; The solid drug-delivery preparation can add solid preparation adjuvant commonly used such as excipient glucose, lactose, cellulose etc. in preparation, also can add lubricant Polyethylene Glycol, magnesium stearate etc., and the required adjunct ingredients of solid preparation such as binding agent, correctives, again by operation molding such as mixing, granulations.The effective dose of the active substance in above-mentioned these preparations is the amount that diabetic symptom is obviously reduced, research worker with routine techniques can be determined the most effective dosage and the time consideration administering mode of the reagent that this invention provides, drug metabolism, and some other pharmacokinetic parameter drug distribution for example, clearance rate etc.Reagent provided by the present invention can also and other reagent conventional antidiabetic drug medicine administering drug combinations for example so that the onset diabetes degree effectively reduces.

The present invention carries out illustration by the diabetes model of in the body high glucose and high fat being induced.Animal herein includes, but are not limited to: mice, rat, performing animal includes, but are not limited to cat, Canis familiaris L., and some other animal for example but be not limited to cattle, sheep, pig, horse, primate for example but be not limited to monkey and people.

The present invention proposes the new application of carrageenan in preparation treatment diabetes medicament; the insulin resistant that the chronic inflammatory disease that the activated macrophage that this medicine can protect body to avoid the reason generations such as obesity causes causes, thereby outbreak or the sx↑ of inhibition diabetes.Carrageenan is obtained good curative effect in the animal model that high glucose and high fat is induced, simultaneously, medicine used in the present invention is easy to obtain, and is cheap, and stable in properties is convenient to storage and transport, has broad application prospects.

 

The specific embodiment

The zoopery example

(treatment of the diabetes model that carrageenan injection solution preparation is induced high glucose and high fat)

It is for subsequent use that the carrageenan of different molecular weight is made into the 2.0mg/ml injection with physiological saline solution, regulates pH value to 7.0 with 10 mol/L NaOH solution.Get 42 of female new zealand white rabbits, body weight 1.8 kg-2.0 kg are divided into 7 groups at random with animal, and 6 every group, i.e. Normal group, diabetic model group, respectively with the treatment group of the carrageenan treatment of different molecular weight.Normal group utilizes common feedstuffs (rabbit standard common feedstuff, Standard Laboratory Chow for Rabbits, Shanghai Shengwang Experimental Animal Ranch (P.R.China) company) to raise.Model group animal and each treatment experimental group is supplied with the high lipolysaccharide feedstuff that contains the sucrose of 10% Adeps Sus domestica and 37% above-mentioned rabbit in the standard test feedstuff, and the lumbar injection carrageenan is treated, and the model group of drug treatment is not injected isopyknic normal saline.After (after 0 week), 4 weeks after the experiment beginning, after 8 weeks, after 12 weeks, after 16 weeks, after 20 weeks and after 24 weeks, make and respectively organize rabbit and go on a hunger strike a night, take a blood sample from arteria auricularis, use the commercially available glucose assays test kit that utilizes enzyme process (Glucose Determination Kit(Glucose oxidase-peroxidase method), Shanghai Rongsheng Biotech Inc.(P.R.China) company makes), measure the concentration of glucose (mg/dl) in the blood plasma, experimental result is as shown in table 1:

Table 1: the evaluation of pesticide effectiveness of carrageenan

Group	0 week	4 weeks	8 weeks	12 weeks	16 weeks	20 weeks	24 weeks
								Normal group	54	61	48	72	58	67	55
Model group	51	109	118	122	125	134	134
								7.2 KD carrageenan	57	99	102	118	124	168	172
13 KD carrageenans	57	88	83	91*	94*	85*	71*
								40 KD carrageenans	62	90	85	89*	83*	78*	81*
70 KD carrageenans	50	98	91	88*	86*	78*	87*
								120 KD carrageenans	63	77	88	67*	72*	81*	62*

Data are shown with the form of meansigma methods that all significant difference is determined by the ANOVA check.* represent P≤0.05.Therapeutic outcome shows that the diabetes animal model blood sugar level after the carrageenan treatment obviously reduces, and illustrates and uses carrageenan can treat preferably diabetes.

Claims (2)

1. the application of carrageenan in preparation treatment diabetes medicament.

2. application according to claim 1 is characterized in that: described carrageenan molecule amount is 7.2 KD ~ 120 KD.