KR20130117244A - Composition comprising the extract of paecilomyces japonica for improving insulin resistance - Google Patents

Abstract

PURPOSE: A composition containing a Paecilomyces japonica extract is provided to prevent and treat insulin resistance and insulin resistance syndrome thereby and to effectively control hypertension caused by type 2 diabetes. CONSTITUTION: A pharmaceutical composition for treating insulin resistance contains 1-5 wt% of a Paecilomyces japonica extract as an active ingredient. The extract is a hot water extract. A pharmaceutical composition for preventing or treating type 2 diabetes contains the extract as an active ingredient.

Description

Composition comprising the extract of Paecilomyces japonica for improving insulin resistance}

The present invention relates to a composition for improving insulin resistance, containing an extract of Snow Cordyceps sinensis as an active ingredient.

In diabetes, type 1 diabetes and pancreatic beta cells are destroyed and the insulin released from the pancreas is not enough or even more than normal, but blood sugar rises (called insulin resistance). There is type 2 diabetes, in which the blood sugar rises because only a small amount of insulin is released from the pancreas.

Insulin resistance is a major cause of type 2 diabetes with a reduced insulin action in peripheral tissues (Kahn, SE, Diabetologia , 46 , pp3-19, 2003). In diabetes, hormonal imbalances, including insulin, are characteristic of hyperglycemia due to abnormal physiological metabolic control functions such as protein, lipid and electrolyte metabolism including carbohydrates (Gonuth, SM, Ann . Intern . Med . , 79 , pp812-822, 1973) Continued hyperglycemia causes blood circulation disorders, retinal damage, neuronal damage, renal failure and vascular complications (UK Prospective Diabetes Study (UKPDS) Group, Lancet , 352 , pp837853, 1998).

Most people with type 2 diabetes are obese or moderate in physique, have less severe symptoms, and have less complications, such as ketoacidosis, compared to type 1 diabetes. In many cases, type 2 diabetes can be treated with diet, exercise and eating hypoglycemic drugs, but sometimes insulin injections can be used to control blood sugar.

Korean Patent No. 10-0711028 discloses a composition for preventing and treating obesity and type 2 diabetes, including juniper extract or cedrol, and Korean Patent Laid-Open No. 2012-0004658, a second containing extract of yacon leaf fermented tea A composition for preventing or treating type diabetes is provided. Korean Patent No. 2009-0081860 discloses a pharmaceutical composition for treating type 2 diabetes, including processed aloe vera gel.

Cordyceps sinensis (冬蟲夏草) comes from the meaning of insects in winter and mushrooms in summer. In other words, cordyceps fungi, a type of fungus contained in the soil, mainly live at a time of high temperature and humidity. When the host insect dies while entering the body through the insect's respiratory organs, digestive organs, joints, etc., eating nutrients, and growing, the fruiting body is formed on the epidermis of the insect. Until now, it is a type of insect parasitic medicinal mushroom that has a characteristic of maintaining its shape like a mummy without perishing, and belongs to the genus Cordyceps sinensis supernatant. Cordyceps originally refers to Cordyceps sinensis from the larvae of the bat moth, but today it refers to all the mushrooms from spiders, cicadas and fungi as well as insects. In addition to the Cordyceps genus Podonectria, Torrubiella, Isaria, Paecilomyces, Gibellular and Hymenostilbe , Hirsutella, Neocodycept

There are various cordyceps such as Neocordyceps, Shimizuomyces, Sphaerocordyceps and Tilachlidiopsis.

Among the various Cordyceps sinensis, research has been actively conducted on Snow Flower Cordyceps. Korean Patent No. 10-0932836 proposes a snowflower Cordyceps sinensis extract that inhibits the activity of a Kadipsin K, and Korean Patent No. 10-0559998 proposes a food composition comprising the cicada larva Snowflower Cordyceps sinensis as an active ingredient, and Korean Patent Registration No. 10-1059021 proposes a method for producing a decapitated S. dep. Derived from Snow Cordyceps sinensis and a composition for improving obesity using the same as an active ingredient. Korean Patent No. 10-0447101 proposes a Cordyceps sinensis extract having a thrombolytic action and a thrombolytic enzyme isolated therefrom. In addition, the effect of Snow Cordyceps sinensis on lipid metabolism of rats fed high fat diet [Food Sci Nutr. 2003; 32: 238-243. However, there has been no report on the effect of improving the insulin resistance of the extract of Snow Cordyceps sinensis.

Therefore, the present inventors completed the present invention by confirming that the extract of Snow Cordyceps sinensis has an effect of improving insulin resistance while studying the pharmaceutical material of Snow Cordyceps sinensis. Therefore, it is an object of the present invention to provide a pharmaceutical composition for improving insulin resistance, which comprises an extract of Snow Cordyceps sinensis as an active ingredient.

It is another object of the present invention to provide a pharmaceutical composition for treating type 2 diabetes, comprising an extract of Snow Cordyceps sinensis as an active ingredient.

In order to achieve the object of the present invention as described above, the present invention is a snow cordyceps ( Paecilomyces) japonica ) provides a composition for improving insulin resistance comprising the extract as an active ingredient.

In one embodiment of the present invention, the snow Cordyceps sinensis extract may be a hot water extract.

In one embodiment of the present invention, the snow Cordyceps sinensis extract may be characterized in that it is included in the weight percent of 1 ~ 5% with respect to the total weight of the composition.

The present invention also provides a composition for the prevention or treatment of type 2 diabetes comprising the extract of Paecilomyces japonica as an active ingredient.

The present invention also provides a dietary supplement for improving insulin resistance, comprising an extract of Paecilomyces japonica as an active ingredient.

The composition comprising the extract of the Snow Cordyceps sinensis of the present invention exhibits the effect of preventing and treating insulin resistance and insulin resistance syndrome thereby, and can be effectively used for the management of hyperglycemia due to type 2 diabetes. In addition to the diabetes treatment currently relying on chemical oral hypoglycemic agents and insulin therapy, it can be prepared as a dietary supplement, as well as pharmaceuticals, and can be usefully provided to various diabetics.

The present invention is characterized by providing a composition for improving insulin resistance and treating type 2 diabetes, including an extract of Snow Cordyceps sinensis as an active ingredient. The name Cordyceps sinensis has been related to the invasion of cordyceps, forming fungal nuclei in the body of insects in winter, and sprouting like grass in summer. Spores and mycelium of Cordyceps fungus invade insects, fungi and seeds of plants, and use the substances in the host as nutrients to form endogenous nuclei and then form fruiting bodies. To date, more than 800 species of Cordyceps invades insects worldwide. It has recently been demonstrated that Cordyceps sinensis has a very powerful immune function-enhancing and anti-cancer activity, and various documents have reported the effect of hypoglycemic activity. Paecilomyces japonica is a fungus of the genus Cordyceps fungus Cordyceps sinensis, also called moth flower cordyceps.

The present invention is effective in the treatment and prevention of the second diabetes by confirming the effect of the above-mentioned snow Cordyceps sinensis extract having the above-described characteristics improves insulin resistance by increasing the adiponectin, a hormone secreted from adipose tissue, and has a blood sugar reducing effect. Was first identified.

More specifically, according to one embodiment of the present invention, the blood glucose was measured in the diabetic animal model db / db mice was significantly reduced blood sugar in the group fed the dietary supplement containing the Snow Cordyceps sinensis extract of the present invention compared to the control group It was confirmed that, through this it can be inferred that the snow Cordyceps sinensis extract of the present invention has an effect of lowering blood sugar.

In addition, according to another embodiment of the present invention, as a result of measuring the serum insulin concentrations of the control group and the snow Cordyceps sinusitis group, there was no significant difference between the two groups. HOMA-IR is an indicator of insulin resistance. As a result of measuring HOMA-IR of the control group and the Snow Clover group, the HOMA-IR of the Snow Clover group was significantly decreased compared to the control group. In addition, adiponectin is a hormone secreted from adipose tissue, which improves insulin resistance, and it was confirmed that the concentration of serum adiponectin of the Snow Cordyceps group was significantly higher than that of the control group. It showed an effect to improve, which was confirmed in part due to the increase in adiponectin.

That is, the composition of the present invention having the above characteristics can be usefully used to improve insulin resistance and to prevent and treat type 2 diabetes mellitus, Paecilomyces japonica ) can be used as a pharmaceutical composition for improving insulin resistance, including the extract as an active ingredient, Paecilomyces japonica ) can also be used as a composition for treating type 2 diabetes comprising the extract as an active ingredient.

Snow Cordyceps sinensis extract according to the present invention may be obtained by extracting and separating from nature using the extraction and separation methods known in the art, the 'extract' as defined in the present invention using the appropriate solvents It is extracted from, for example, may include all of the hot water extract of Snow Cordyceps sinensis, soluble polar solvent extract or non-polar solvent soluble extract.

As a suitable solvent for extracting the extract from the snow Cordyceps sinensis, any solvent that is acceptable in the art may be used, and water or an organic solvent may be used. Examples of the solvent include alcohols having 1 to 4 carbon atoms, acetone, ether, and the like, including purified water, methanol, ethanol, propanol, isopropanol, butanol, Various solvents such as benzene, chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane may be used alone or in combination. But is not limited to.

As the extraction method, any one of the methods such as hot water extraction method, cold extraction method, reflux cooling extraction method, solvent extraction method, steam distillation method, ultrasonic extraction method, elution method and compression method can be selected and used. In addition, the desired extract may be further subjected to a conventional fractionation process or may be purified using a conventional purification method. There is no limitation on the preparation method of the snow Cordyceps sinensis extract of the present invention, any known method can be used.

For example, the snow Cordyceps sinensis extract included in the composition of the present invention may be prepared in a powder state by an additional process such as distillation under reduced pressure or freeze drying or spray drying, which is extracted by the hydrothermal extraction or solvent extraction. have. Further, the primary extract can be further purified by using various chromatographies such as silica gel column chromatography, thin layer chromatography, high performance liquid chromatography and the like, You can get it.

Therefore, in the present invention, the snow Cordyceps sinensis extract is a concept including all the extracts, fractions and purified products obtained in each step of extraction, fractions or purification, their dilutions, concentrates or dried products.

According to a specific embodiment of the present invention, the preparation of the Snow Cordyceps Sinensis extract of the present invention is carried out as follows.

Snow Cordyceps sinensis extract of the present invention was added for 20 hours distilled water to commercially sold Snow Cordyceps sinensis and then extracted at 90 ^o C for 8 hours. The extract was concentrated under reduced pressure at 80 ^° C. using a vacuum rotary concentrator and then lyophilized. The yield of the extract was 30.1%. The extract was used for the experiment while stored at -20 ℃.

The composition of the present invention containing such a snow Cordyceps sinensis extract as an active ingredient may be a pharmaceutical composition.

The pharmaceutical composition of the present invention can be prepared by using pharmaceutically acceptable and physiologically acceptable adjuvants in addition to the above-mentioned active ingredients. Examples of the adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, A lubricant or a flavoring agent can be used.

The pharmaceutical composition may be formulated into a pharmaceutical composition containing at least one pharmaceutically acceptable carrier in addition to the above-described active ingredients for administration.

The pharmaceutical composition may be in the form of granules, powders, tablets, coated tablets, capsules, suppositories, liquids, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation into tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Also, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included as a mixture. Suitable binders include but are not limited to natural and synthetic gums such as starch, gelatin, glucose or beta-lactose, corn sweeteners, acacia, trackercance or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum and the like. Acceptable pharmaceutical carriers for compositions that are formulated into a liquid solution include sterile water and sterile water suitable for the living body such as saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.

In one embodiment of the present invention, the Snow Cordyceps Sinensis extract of the present invention may be included in 0.00001 to 30% by weight based on the total weight of the composition.

The composition of the present invention may also be a food composition, and the food composition may contain various flavors or natural carbohydrates as an additional ingredient, as well as a conventional food composition, in addition to containing the extract of snow cauliflower.

Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. The above-described flavors can be advantageously used as natural flavorings (tau martin), stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.).

The food composition of the present invention can be formulated in the same manner as the above pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolates, foods, confectionery, pizza, ram noodles, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes, .

In addition, the food composition is an active ingredient snow extracts of the various kinds of nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavoring agents, coloring and neutralizing agents (cheese, chocolate, etc.), pectic acid and its Salts, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like. In addition, the food composition of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks.

The health functional food of the present invention may be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills and the like for the purpose of improving insulin resistance and preventing and treating diabetes.

In the present invention, the term " health functional food " refers to foods manufactured and processed using raw materials or ingredients having useful functions in accordance with Law No. 6727 on Health Functional Foods. Or to obtain a beneficial effect in health use such as physiological action.

The health functional food of the present invention may include a conventional food additive, and the suitability as a food additive, unless otherwise specified, in accordance with the General Regulations of the Food Additives and General Test Methods approved by the Food and Drug Administration, etc. Judging by the standards and standards.

Examples of the items listed in the above-mentioned "food additives" include chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as persimmon extract, licorice extract, crystalline cellulose, high color pigment and guar gum; L-glutamic acid sodium preparations, noodle-added alkalis, preservative preparations, tar coloring preparations and the like.

For example, the health functional food in the form of tablets is a mixture of excipients, binders, disintegrants and other additives of the snowweed Cordyceps sinensis extract, which is the active ingredient of the present invention, is granulated in a conventional manner, and then compressed with a lubricant and the like. Or the mixture can be directly compression molded. In addition, the health functional food in the form of tablets may contain a mating agent and the like as necessary.

Hard capsules among the health functional foods in the form of capsules may be prepared by filling a mixture of additives, such as the snow Cordyceps sinensis extract, which is the active ingredient of the present invention, in a conventional hard capsule, and the soft capsules are the extracts of Snow Cordyceps sinensis, etc. The mixture mixed with the additive of may be prepared by filling in a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.

The health functional food in the form of a cyclic form can be prepared by molding a mixture of a snowweed Cordyceps sinensis extract, an excipient, a binder, a disintegrant, and the like, according to a known method, and as a sugar or other skin repellent agent, if necessary. It may be avoided, or the surface may be coated with materials such as starch, talc.

The health functional food in the form of granules can be prepared into granules by a conventionally known method in which a mixture of snowweed Cordyceps sinensis extract, an active ingredient of the present invention, an excipient, a binder, a disintegrant, and the like, and a flavoring agent and a copper, are necessary. And the like.

The health functional food may be a beverage, a meat, a chocolate, a food, a confectionery, a pizza, a ramen, a noodle, a gum, a candy, an ice cream, an alcoholic beverage, a vitamin complex and a health supplement food.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are for further illustrating the present invention, and the scope of the present invention is not limited to these examples.

Statistical processing

All measurements were expressed as mean ± standard error (mean ± SEM). The significance test between the control group and the Snow Cordyceps sinensis group was performed by Student's t-test (p <0.05).

< Example  1>

Snow Cordyceps Heat number  Preparation of extract

20 times distilled water was added to a commercially available Snow Caterpillar sec. And extracted at 90 ^o C for 8 hours. The extract was concentrated under reduced pressure at 80 ^o C using a vacuum rotary condenser and then lyophilized. The yield of the extract was 30.1%. The extract was used for the experiment while stored at -20 ℃.

< Example  2>

Body weight and Dietary intake  Measure

① Experimental Animal and Experimental Design

Four-week-old male C57BL / Ks-db / db mice (n = 14) were purchased and after one week of adaptation, the animals were divided into two groups according to the egg mass method. The AIN-93G diet was used as a control group and the snow Cordyceps sinensis herb hot water extract was fed as a 1% level of the diet for 7 weeks. The dietary composition is shown in Table 1 below. Diet and drinking water freely ( ad libitum ), and the temperature and humidity of the feeding room were maintained at 20-25 ℃ and 50-60%, respectively, and the contrast was turned on and off every 12 hours. During the experiment, body weight and dietary intake were measured twice a week. Seven weeks after the start of the diet, the animals were fasted for 12 hours and the animals were sacrificed by cardiac sampling. Blood was centrifuged at 3,000 × g for 15 minutes and then serum was collected and stored at -70 ° C.

Dietary composition Furtherance Control Diet (%) Snow Cordyceps Sinensis Diet (%) Corn starch ^{1 )} 39.75 38.75 Casein ^{2 )} 20.00 19.22 Dextrinized starch 13.20 13.20 Sucrose ^{3 )} 10.00 10.00 a-cellulose ^{4 )} 5.00 Mineral mixtures ^{5 )} 3.50 3.50 Vitamin mixtures ^{5 )} 1.00 1.00 L-cystine ^{5 )} 0.30 0.30 Choline Bitartrate ^{3 )} 0.25 0.25 Tert-Butylhydroquinone 0.0014 0.0014 Soybean oil ^{6 )} 7.0 6.94 Snow Cordyceps Sinensis Extract - 1.00 ¹⁾ Target company, Korea
²⁾ Murry goulburn Co., Australia
³⁾ Samyangsa, Korea
⁴⁾ Sigma, USA
⁵⁾ ICN Biochemical, USA
⁶⁾ CheilJedang, Korea

② Measurement of changes in weight and dietary intake

As shown in Table 2, after one week of adaptation to four-week-old db / db mice, the control diet and the Snow Cordyceps sinensis extract-containing diet for 7 weeks, the weight of the control group and Snow Cordyceps is 40.2 ± 2.1, 40.6, respectively. ± 2.6 g. The dietary intake was 4.2 ± 0.3 g / day and 4.3 ± 0.4 g / day in the control group and the Snow Cordyceps sinensis group, respectively. Body weight and dietary intake were not significantly different between the two groups.

Weight and Dietary Intake of Control and Snow Cordyceps in Diabetic Animal Models Control group Snow Flower Cordyceps Body weight (g) ^{1 )} 40.2 ± 2.1 ²⁾ 40.6 ± 2.6 ^{ns3 )} Dietary intake (g / day) 4.2 ± 0.3 4.3 ± 0.4 ^{ns 1)} Weight after 7 weeks of dietary intake
²⁾ Mean ± SEM
³⁾ not significant

< Example  3>

Measurement of blood sugar control effect and insulin resistance improvement effect

<3-1> Confirmation of blood sugar control effect

Blood glucose was measured by enzyme method. Blood glycated hemoglobin concentration was measured by column chromatography. As a result, referring to Table 3, the blood glycated hemoglobin concentration of the control group and the Snow Clover group was 7.9 ± 0.3, 7.0 ± 0.2%, respectively, and the blood glycated hemoglobin concentration of the Snow Clover group was significantly lower than the control group (p <0.05). The blood sugar levels of the control and snow Cordyceps subgroups were 462.5 ± 22.4 and 368.0 ± 21.0 mg / dL, respectively, and the blood sugar levels of the Snow Cordyceps subgroups were significantly lower than those of the control group (p <0.01).

<3-2> Insulin resistance improvement effect measurement

Serum insulin concentrations were measured by radioimmunoassay. Homeostasis model assessment for insulin resistance (HOMA-IR), an index of insulin resistance, was calculated as [{glucose (mmol / L) × insulin (μU / mL)} / 22.5] (Haffner, SM, Miettinen, H., Stern, MP Diabetes Care , 20 , pp 10871092, 1997). Serum adiponectin concentration was measured by ELISA method.

As a result, referring to Table 3, the serum insulin concentrations of the control group and the Snow Clover subgroup were 71.0 ± 3.6 and 64.2 ± 3.3 μU / mL, respectively, and there was no significant difference between the two groups. HOMA-IR of the control group and the Snow Cordyceps group were 80.8 ± 5.1 and 58.0 ± 3.9, respectively, and the HOMA-IR of the Snow Cordyceps group was significantly decreased compared to the control group (p <0.01). HOMA-IR is an indicator of insulin resistance.

Serum adiponectin concentrations of the control group and the Snow Clover group were 9.6 ± 0.4 and 11.4 ± 0.5 ng / mL, respectively, and the adiponectin concentration of the Snow Clover group was significantly higher than that of the control group (p <0.05).

Blood sugar, glycated hemoglobin, insulin, HOMA-IR and adiponectin Control group Snow Flower Cordyceps Glycated hemoglobin (%) ¹⁾ 7.9 ± 0.3 7.0 ± 0.2 ^{* 2)} Blood sugar (mg / dL) 462.5 ± 22.4 368.0 ± 21.0 ^{** 3)} Insulin (μU / mL) 71.0 ± 3.6 64.2 ± 3.3 ^{ns4 )} HOMA-IR 80.8 ± 5.1 58.0 ± 3.9 ^** Adiponectin (ng / mL) 9.6 ± 0.4 11.4 ± 0.5 ^{* 1)} Mean ± SEM
²⁾ p <0.05
³⁾ p <0.01
⁴⁾ not significant

Therefore, through these experimental results, the present inventors have found that the hydrothermal extract of the Cordyceps sinensis according to the present invention can be used for preventing or treating diseases that may be caused by insulin resistance.

So far I looked at the center of the preferred embodiment for the present invention. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

Claims (7)

Snowflake Cordyceps ( Paecilomyces) japonica ) A pharmaceutical composition for improving insulin resistance comprising the extract as an active ingredient. The method of claim 1,
The extract is a pharmaceutical composition for improving insulin resistance, characterized in that the hot water extract of Snow Cordyceps sinensis. The method of claim 1,
The snow Cordyceps sinensis extract is a pharmaceutical composition for improving insulin resistance, characterized in that contained in 1% to 5% by weight relative to the total weight of the composition. Snowflake Cordyceps ( Paecilomyces) japonica ) A pharmaceutical composition for preventing or treating type 2 diabetes, comprising the extract as an active ingredient. 5. The method of claim 4,
The extract is a pharmaceutical composition for the prevention or treatment of type 2 diabetes, characterized in that the hot water extract of Snow Cordyceps sinensis. The method of claim 1,
The snow Cordyceps sinensis extract is a pharmaceutical composition for the prevention or treatment of type 2 diabetes, characterized in that contained in 1 to 5% by weight based on the total weight of the composition. Snowflake Cordyceps ( Paecilomyces) japonica ) Health functional food for improving insulin resistance comprising the extract as an active ingredient.