Application of carob bean extract in medicine for improving glycometabolism female polycystic ovarian syndrome

Abstract

The invention belongs to the technical field of plant extracts, and particularly relates to application of a carob bean extract in a medicine for improving glycometabolism / female polycystic ovarian syndrome. The invention discloses a pharmaceutical composition for improving glycometabolism female polycystic ovarian syndrome. The pharmaceutical composition is prepared from a carob bean extract, baicalein, cedrol, bioactive peptide, biological polysaccharide and auxiliary materials. The composition disclosed by the invention has the effects of reducing blood sugar, reducing blood fat and improving an insulin function, and also has the effects of resisting oxidation, enhancing immunity and the like, and the substances are combined for use, so that a synergistic interaction effect is achieved, and the effect of improving / treating the abnormal glucose metabolism related female polycystic ovarian syndrome is further improved.

Description

Technical Field

[0001] The invention belongs to the technical field of plant extracts, and in particular relates to an application of a carob extract in a drug for improving sugar metabolism / female polycystic ovary syndrome. Background Art

[0002] Carob, also known as long bean, is distributed along the Mediterranean coast, California and other places, and is mainly planted in Guangxi, Sichuan, Yunnan and Guangdong. Carob contains natural polysaccharides, multiple vitamins, proteins and trace elements, and has extremely high nutritional value and medicinal value. It is suitable for long-term consumption by patients with stomach and heart diseases, and it also has a good effect on preventing colds and coughs. Carob extract can be obtained by extracting carob with solvent and concentrating under reduced pressure. Carob extract is a light green liquid that is easily soluble in water and ethanol. Carob extract can be used as a raw material for dietary supplements. Its main functions are to regulate hormone balance, improve metabolic syndrome, improve polycystic ovary syndrome and lower blood sugar.

[0003] Polycystic ovary syndrome (PCOS) is a common endocrine disease associated with reproductive and metabolic disorders in women, which can cause women's health problems including endocrine, glucose and lipid metabolism, reproduction, and mental health. The main clinical features of PCOS are menstrual disorders, hyperandrogenism, and polycystic ovarian changes, often accompanied by obesity and insulin resistance. It is the most common cause of menstrual disorders in women of childbearing age and the main cause of anovulatory infertility. In addition, in addition to causing symptoms such as decreased fertility and obesity in women of childbearing age, PCOS also has significant metabolic effects. If not corrected in time, it will increase the risk of diabetes, cardiovascular disease, endometrial cancer and other diseases. Summary of the invention

[0004] The primary purpose of the present invention is to provide an application of carob extract in a drug for improving sugar metabolism / polycystic ovary syndrome in women. By combining the carob extract with a variety of substances, the effect of the carob extract on improving sugar metabolism and polycystic ovary syndrome in women can be increased.

[0005] To this end, the present invention provides the following technical solutions.

[0006] One aspect of the present invention provides a pharmaceutical composition for improving sugar metabolism in women with polycystic ovary syndrome, the pharmaceutical composition comprising: carob extract, baicalein, cedrol, bioactive peptides, biopolysaccharides and excipients.

[0007] As a preferred embodiment of the present invention, the pharmaceutical composition comprises, by weight: 20-30 parts of carob extract, 1-3 parts of biopolysaccharides, 0.5-1 part of baicalein, 0.5-1 part of cedrol, 0.1-0.5 part of bioactive peptides and 80-120 parts of excipients.

[0008] As a preferred embodiment of the present invention, the mass content of D-chiro-inositol in the carob extract is ≥95%.

[0009] As a preferred embodiment of the present invention, the biological polysaccharide is selected from one or a mixture of two or more of wolfberry polysaccharide, tremella polysaccharide, macroalgae polysaccharide, lemon peel polysaccharide, blackberry polysaccharide and honeysuckle polysaccharide.

[0010] As a preferred embodiment of the present invention, the bioactive peptide is selected from one or a mixture of two or more of leech active peptides, abalone active peptides, milk-derived active peptides, and silkworm pupa-derived active peptides.

[0011] As a preferred embodiment of the present invention, the milk-derived active peptide is selected from any one of horse milk-derived active peptides, bovine milk-derived active peptides, and goat milk-derived active peptides, or a mixture of two or more thereof.

[0012] As a preferred embodiment of the present invention, the auxiliary material is selected from one or a mixture of two or more of a diluent, a flavoring agent, a lubricant, a glidant, a disintegrant, and a binder.

[0013] As a preferred embodiment of the present invention, the diluent is selected from one or a mixture of two or more of pregelatinized starch, mannitol, calcium hydrogen phosphate, microcrystalline cellulose, and xylitol.

[0014] As a preferred embodiment of the present invention, the flavoring agent is selected from one or a mixture of two or more of mint powder flavor, lemon powder flavor, strawberry powder flavor, cream powder flavor, and banana powder flavor.

[0015] As a preferred embodiment of the present invention, the lubricant is selected from one or a mixture of two or more of magnesium stearate, micro-powder silica gel, calcium silicate and talc.

[0016] As a preferred embodiment of the present invention, the glidant is selected from silicon dioxide.

[0017] As a preferred embodiment of the present invention, the disintegrant is selected from one or a mixture of two or more of dry starch, microcrystalline cellulose, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, and polyvinyl pyrrolidone.

[0018] As a preferred embodiment of the present invention, the adhesive is selected from one or a mixture of two or more of starch slurry, povidone, gelatin, gum arabic, sodium alginate, and polyethylene glycol.

[0019] As a preferred embodiment of the present invention, the pharmaceutical composition is in the form of tablets, capsules, pills, mixtures, gels, ointments, granules, powders, pastes, granules, pills, oral liquids, pills, injections or injections.

[0020] Another aspect of the present invention also provides a method for preparing the pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome as described above, the preparation method comprising the following steps: The raw materials are weighed according to the proportions and mixed evenly, and then made into a suitable form as required to obtain a pharmaceutical composition for improving sugar metabolism in female polycystic ovary syndrome.

[0021] Another aspect of the present invention provides a use of the pharmaceutical composition for improving glucose metabolism in female polycystic ovary syndrome as described above in the preparation of a drug for improving and / or treating glucose metabolism in female polycystic ovary syndrome.

[0022] By means of the above technical solution, the present invention has at least the following advantages: 1. The present invention uses carob extract, baicalein, cedrol, bioactive peptides, and biopolysaccharides as main active substances, and obtains a composition through reasonable compatibility of these substances under the action of auxiliary materials. The composition can effectively improve the insulin activity of polycystic ovary syndrome, regulate endocrine and improve hormone balance, make the patient's menstruation regular, ovulate normally, hormones return to normal levels, improve the patient's fertility level, reduce the risk of diabetes, cardiovascular disease, endometrial cancer and other diseases, that is, it has a significant effect on improving or treating polycystic ovary syndrome in women with sugar metabolism.

[0023] 2. The bioactive peptides used in the present invention are selected from one or a mixture of two or more of leech active polypeptides, abalone active peptides, horse milk-derived active peptides, and silkworm pupa-derived active peptides. The biopolysaccharides used are selected from one or a mixture of two or more of wolfberry polysaccharides, tremella polysaccharides, macroalgae polysaccharides, lemon peel polysaccharides, blackberry polysaccharides, and honeysuckle polysaccharides. All of the above substances have the effects of lowering blood sugar, lowering blood lipids, and improving insulin function. They also have the effects of anti-oxidation and enhancing immunity. By combining the above substances with carob extract, baicalin, and cedrol, a synergistic effect is achieved, thereby further improving the effect of improving / treating female polycystic ovary syndrome related to abnormal glucose metabolism.

[0024] The above description is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention and implement it according to the contents of the specification, the preferred embodiments of the present invention are described in detail as follows. DETAILED DESCRIPTION

[0025] In order to make the technical means, creative features, objectives and effects of the present invention easy to understand, the technical solutions in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0026] Carob bean extract is obtained by solvent extraction and reduced pressure concentration using carob as raw material. Carob bean extract (Carobbean extract) is a light green liquid that is easily soluble in water and ethanol. Carob bean extract can be used as a raw material for dietary supplements. The main functions are to regulate hormone balance, improve metabolic syndrome, improve polycystic ovary syndrome and lower blood sugar. Among them, the main active substance in carob bean extract is D-chiro-inositol. D-chiro-inositol (DCI) is one of the nine isomers of inositol that has optical activity. Through recent studies, it has been found that D-chiro-inositol (DCI) has the function of promoting liver lipid metabolism, in addition to inositol, it also has insulin sensitization, lowering blood sugar, improving the ovulation of patients with polycystic ovary syndrome (PCOS), regulating hormone balance, improving menstrual disorders, and special physiological functions of anti-oxidation, anti-aging and anti-inflammatory. Unless otherwise specified, the carob bean extract described in the present invention is purchased from Shandong Aimi Biotechnology Co., Ltd., wherein the mass content of D-chiro-inositol is ≥95%.

[0027] Baicalein is one of the flavonoid compounds with the highest content in Scutellaria baicalensis. It has multiple effects. For example, baicalein has the effects of reducing cerebral vascular resistance, improving cerebral blood circulation, increasing cerebral blood flow and anti-platelet aggregation. It is clinically used for the treatment of paralysis after cerebrovascular disease. In addition, Scutellaria baicalensis also has a wider antibacterial spectrum, and has inhibitory effects on Shigella dysenteriae, Corynebacterium diphtheriae, Pseudomonas aeruginosa, Staphylococcus, Streptococcus, Pneumococcus and meningococcus. Unless otherwise specified, the baicalein described in the present invention is purchased from Yunnan Siji Biological Co., Ltd.

[0028] Cedrol is extracted from Atlantic cedar and is a natural sesquiterpene alcohol with multiple pharmacological activities. Studies have been conducted on cedrol isolated from the essential oil of Nitraria sibiricum, and the results show that cedrol exhibits significant inhibitory activity against Staphylococcus aureus, Bacillus subtilis, and Salmonella typhimurium. Several other studies have shown that it can also be used for the treatment of cancer. For example, cedrol can induce colorectal cancer cell cycle arrest and enhance cell apoptosis, and is considered to be an effective drug for the treatment of colorectal cancer; cedrol can inhibit the growth of glioblastoma and induce intracellular DNA damage, thereby inhibiting its development. In addition, studies have shown that cedrol has an inhibitory effect on the activation of androgen receptor (AR) induced by dihydrotestosterone (DHT) in cultured fetal rat dermal fibroblasts in vitro. The results show that cedrol has a certain regulatory effect on the level of male hormones. Unless otherwise specified, the cedrol (purity> 98%) described in the present invention is purchased from Shanghai TCI Chemical Industry Development Co., Ltd.

[0029] Bioactive peptides (BAPs) are peptide sequences with certain biological activities. According to different sources, bioactive peptides can be divided into exogenous bioactive peptides and endogenous bioactive peptides. Exogenous bioactive peptides refer to bioactive peptides outside the human body, that is, natural bioactive peptides existing in natural animals, plants and microorganisms, as well as bioactive peptides produced after degradation of animal and plant proteins. Endogenous bioactive peptides refer to bioactive peptides produced by enzymatic hydrolysis in the human body and existing in the human body, such as hormone peptides such as insulin and adrenocorticotropic hormone, neuropeptides such as endorphins and enkephalins in the human body. According to the different effects of bioactive peptides on the body, their functions can be roughly divided into antioxidant peptides, blood pressure lowering peptides, anti-inflammatory peptides, anticancer peptides, blood sugar lowering peptides, lipid-lowering peptides, antimicrobial peptides, anti-fatigue peptides, immunomodulatory peptides, muscle synthesis and performance enhancement peptides, and antifungal peptides. These bioactive peptides play an important role in maintaining and restoring the health of the body. Dairy BAPs are mainly derived from casein and whey protein. Casein itself has no active milk protein structure and can be produced through hydrolysis of protein or peptide hydrolyzates, biological fermentation, gastrointestinal digestion, etc. Studies have shown that BAPs have a wide range of biological functions, such as anti-oxidation, hypotensive, hypoglycemic, antibacterial, immunomodulatory and anti-inflammatory. Because of their high specificity, low toxicity, high structural diversity and low molecular weight, they are considered to be ideal substances for use in health products or functional foods.

[0030] In one aspect, the bioactive peptides used in the present invention can be horse milk-derived active peptides, bovine milk-derived active peptides or goat milk-derived active peptides. Unless otherwise specified, the preparation method of the horse milk-derived active peptides described in the embodiment refers to the content described in CN115028706A, which is incorporated herein by reference, and the specific process is: fresh horse milk is centrifuged at 4°C and 10000g for 5min to defatted to obtain defatted horse milk. The defatted horse milk is adjusted to pH 4.2 with HCl in a 45°C water bath, centrifuged at 10000g for 5min, and the precipitate is freeze-dried with a freeze dryer to collect and obtain horse milk casein freeze-dried powder. The horse milk casein freeze-dried powder was prepared into a 100 μg / mL solution with distilled water, sterilized at 115°C for 10 min, cooled to room temperature, and inoculated with activated mixed bacterial liquid (Kazachstania unispora KU530, Lactobacillus helveticus (ATCC: 55163), and Lactobacillus paracasei (Jiangsu Zishi Weikang Biotechnology Co., Ltd.) with a viable count of 1×10 8 CFU / mL) was inoculated into a freeze-dried powder solution of horse milk casein at an inoculation volume of 5% volume fraction for fermentation; the fermentation conditions were: 35°C, a shaker speed of 200 rpm, and a fermentation time of 72 h to obtain a fermentation broth. The pH of the obtained fermentation broth was adjusted to 8, and 8% trypsin (1200U / mg) was added, and the reaction was carried out at 37°C for 6 h to obtain a fermentation hydrolyzate. Subsequently, it was filtered with an ultrafiltration membrane with a cutoff of 1 kDa to obtain a solution of components with a molecular weight of ≤1 kDa. Finally, it was freeze-dried and the freeze-dried powder was collected, which was the horse milk-derived active peptide. The active peptide has a small molecular weight of less than 1 kDa and low immunogenicity, and is very suitable for use in the body. Unless otherwise specified, bovine milk-derived active peptides and goat milk-derived active peptides are prepared in the same way, which will not be repeated here.

[0031] On the other hand, the bioactive peptides used in the present invention can also be abalone active peptides, silkworm pupa-derived active peptides or leech active peptides. Silkworm pupae are the main byproducts of the silk reeling industry and are also one of the new resource foods approved by the Ministry of Health. Silkworm pupae are rich in nutrients such as protein, fat, minerals and vitamins, and are a high-protein, low-calorie edible insect resource, among which silkworm pupa protein is a rich source of active peptides. Studies have shown that active polypeptides derived from silkworm pupae have biological activities such as antibacterial, antihypertensive and antioxidant, can be digested and absorbed in the gastrointestinal tract through food matrices, and play a beneficial function. Unless otherwise specified, the preparation method of the silkworm pupa-derived active peptides described in the embodiment of the present invention is: fresh silkworm pupae are dried, crushed and sieved through an 80-mesh sieve to obtain silkworm pupa powder. The obtained silkworm pupa powder is mixed with deionized water at a material-liquid ratio of 1:20 and ultrasonicated at a power of 800W for 30 minutes to obtain a dispersion. Then, the obtained dispersion was adjusted to pH=10 with sodium hydroxide, and 5% alkaline protease (enzyme activity 200U / mg) and 5% trypsin (1200U / mg) were added, and the reaction was carried out at 50°C for 2h to obtain an enzymatic solution. Then, the solution was filtered with an ultrafiltration membrane with a cutoff of 1kDa to obtain a solution with a molecular weight of ≤1kDa. Finally, the solution was freeze-dried and the freeze-dried powder was collected, which was the active peptide from silkworm pupa.

[0032] Abalone bioactive peptides are marine bioactive peptides prepared from abalone, with the advantages of diverse functions, wide sources, strong specificity, and low toxic and side effects. In addition to protein, abalone visceral protein peptides also contain polysaccharides and trace mineral elements. Studies have shown that abalone protein peptides extracted from abalone and its internal organs have certain anti-tumor, antioxidant, anti-inflammatory and immunomodulatory effects. Leeches, as a traditional Chinese medicine for promoting blood circulation and removing blood stasis, have the functions of breaking blood, removing blood stasis, and dredge menstruation. Leech active polypeptide drugs are more commonly used natural thrombin specific inhibitors, with good anticoagulant, anti-arteriovenous thrombotic effects and low toxic and side effects. Unless otherwise specified, the preparation method of abalone bioactive peptides and leech active polypeptides described in the present invention is consistent with the silkworm pupa source active peptides, which will not be repeated here.

[0033] Unless otherwise specified, the Tremella polysaccharide (purity ≥ 95%) used in the following examples was purchased from Shaanxi Saien Biotechnology Co., Ltd.; Lycium barbarum polysaccharide (purity ≥ 99%) was purchased from Xi'an Youshuo Biotechnology Co., Ltd.; Macroalgae polysaccharide (purity ≥ 98%) was purchased from Fufeng Snow Biotechnology Co., Ltd.; lemon peel polysaccharide (purity ≥ 99%) and blackberry polysaccharide (purity ≥ 99%) were purchased from Lanzhou Waterless Biotechnology Co., Ltd.; other materials, reagents, etc. can be obtained from commercial channels.

[0034] Unless otherwise specified, the preparation process of the honeysuckle leaf polysaccharide used in the following examples is described in the document "Optimization of Honeysuckle Leaf Polysaccharide Extraction Process and Analysis of Antibacterial Activity" published by Shi Ruiwu et al., and will not be repeated here.

[0035] Unless otherwise specified, the percentage content involved in the present invention refers to mass percentage for solid-liquid mixing and solid-solid mixing, and refers to volume percentage for liquid-liquid mixing.

[0036] Unless otherwise specified, the percentage concentrations referred to in the present invention all refer to final concentrations, which refer to the percentage of the added component in the system after the addition of the component.

[0037] The temperature parameters in the present invention, if not specifically limited, allow for both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows the temperature to fluctuate within the precision range controlled by the instrument.

[0038] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods.

[0039] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0040] Embodiment 1: The following raw materials were weighed out according to weight: 25 parts of carob extract, 2 parts of biopolysaccharides (a mixture of wolfberry polysaccharides, tremella polysaccharides, macroalgae polysaccharides, lemon peel polysaccharides, blackberry polysaccharides, and honeysuckle polysaccharides in equal mass ratios), 0.75 parts of baicalein, 0.75 parts of cedrol, 0.3 parts of bioactive peptides (a mixture of leech active peptides, abalone active peptides, horse milk-derived active peptides, and silkworm pupa-derived active peptides in equal mass ratios), and 100 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0041] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0042] Embodiment 2: The following raw materials were weighed out according to weight: 20 parts of carob extract, 3 parts of biopolysaccharides (a mixture of wolfberry polysaccharides, tremella polysaccharides, macroalgae polysaccharides, lemon peel polysaccharides, blackberry polysaccharides, and honeysuckle polysaccharides in equal mass ratios), 0.5 parts of baicalein, 0.5 parts of cedrol, 0.5 parts of bioactive peptides (a mixture of leech active peptides, abalone active peptides, bovine milk-derived active peptides, and silkworm pupa-derived active peptides in equal mass ratios), and 80 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0043] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0044] Embodiment 3: The following raw materials were weighed out according to weight: 30 parts of carob extract, 1 part of biopolysaccharide (a mixture of wolfberry polysaccharide, tremella polysaccharide, macroalgae polysaccharide, lemon peel polysaccharide, blackberry polysaccharide and honeysuckle polysaccharide in equal mass ratio), 1 part of baicalein, 1 part of cedrol, 0.1 part of bioactive peptides (a mixture of leech active peptides, abalone active peptides, goat milk-derived active peptides and silkworm pupa-derived active peptides in equal mass ratio) and 120 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide and sodium alginate in a mass ratio of 1:2:3:1).

[0045] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0046] Embodiment 4: The following raw materials were weighed out according to weight: 25 parts of carob extract, 2 parts of biopolysaccharides (a mixture of wolfberry polysaccharides, tremella polysaccharides, macroalgae polysaccharides, lemon peel polysaccharides, blackberry polysaccharides, and honeysuckle polysaccharides in an equal mass ratio of 1:1:2:2:1:1), 0.75 parts of baicalein, 0.75 parts of cedrol, 0.3 parts of bioactive peptides (a mixture of leech active peptides, abalone active peptides, horse milk-derived active peptides, and silkworm pupa-derived active peptides in an equal mass ratio), and 100 parts of excipients (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0047] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0048] Embodiment 5: The following raw materials were weighed out according to weight: 25 parts of carob extract, 2 parts of biopolysaccharides (a mixture of wolfberry polysaccharide, tremella polysaccharide, macroalgae polysaccharide, lemon peel polysaccharide, blackberry polysaccharide and honeysuckle leaf polysaccharide in equal mass ratio), 0.75 parts of baicalein, 0.75 parts of cedrol, 0.3 parts of bioactive peptides (a mixture of leech active peptides, abalone active peptides, horse milk-derived active peptides and silkworm pupa-derived active peptides in equal mass ratios of 1:1:0.5:2) and 100 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide and sodium alginate in a mass ratio of 1:2:3:1).

[0049] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0050] Comparative Example 1: The only difference between this comparative example and Example 1 is that 25 parts of carob extract are not added, and the rest are consistent with Example 1, namely: The following raw materials were weighed out according to weight: 2 parts of biopolysaccharide (a mixture of wolfberry polysaccharide, tremella polysaccharide, macroalgae polysaccharide, lemon peel polysaccharide, blackberry polysaccharide and honeysuckle leaf polysaccharide in equal mass ratio), 0.75 parts of baicalein, 0.75 parts of cedrol, 0.3 parts of bioactive peptides (a mixture of leech active peptides, abalone active peptides, horse milk-derived active peptides and silkworm pupa-derived active peptides in equal mass ratio) and 100 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide and sodium alginate in a mass ratio of 1:2:3:1).

[0051] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0052] Comparative Example 2: The only difference between this comparative example and Example 1 is that 2 parts of biopolysaccharide are not added, and the rest is consistent with Example 1, namely: The following raw materials were weighed respectively by weight: 25 parts of carob extract, 0.75 parts of baicalein, 0.75 parts of cedarol, 0.3 parts of bioactive peptides (a mixture of leech active peptides, abalone active peptides, horse milk-derived active peptides, and silkworm pupa-derived active peptides in equal mass ratios), and 100 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0053] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0054] Comparative Example 3: The only difference between this comparative example and Example 1 is that 0.75 parts of baicalein is not added, and the rest is consistent with Example 1, that is: The following raw materials were weighed out according to weight: 25 parts of carob extract, 2 parts of biopolysaccharides (a mixture of wolfberry polysaccharides, tremella polysaccharides, macroalgae polysaccharides, lemon peel polysaccharides, blackberry polysaccharides, and honeysuckle polysaccharides in equal mass ratios), 0.75 parts of cedarol, 0.3 parts of bioactive peptides (a mixture of leech active peptides, abalone active peptides, horse milk-derived active peptides, and silkworm pupa-derived active peptides in equal mass ratios), and 100 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0055] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0056] Comparative Example 4: The only difference between this comparative example and Example 1 is that 0.75 parts of cedrol is not added, and the rest is consistent with Example 1, namely: The following raw materials were weighed out according to weight: 25 parts of carob extract, 2 parts of biopolysaccharides (a mixture of wolfberry polysaccharides, tremella polysaccharides, macroalgae polysaccharides, lemon peel polysaccharides, blackberry polysaccharides, and honeysuckle polysaccharides in equal mass ratios), 0.75 parts of baicalein, 0.3 parts of bioactive peptides (a mixture of leech active peptides, abalone active peptides, horse milk-derived active peptides, and silkworm pupa-derived active peptides in equal mass ratios), and 100 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0057] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0058] Comparative Example 5: The only difference between this comparative example and Example 1 is that 3 portions of bioactive peptides are not added, and the rest is consistent with Example 1, namely: The following raw materials were weighed respectively according to weight: 25 parts of carob extract, 2 parts of biopolysaccharides (a mixture of wolfberry polysaccharides, tremella polysaccharides, macroalgae polysaccharides, lemon peel polysaccharides, blackberry polysaccharides, and honeysuckle leaf polysaccharides in equal mass ratios), 0.75 parts of baicalein, 0.75 parts of cedarol, and 100 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0059] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0060] Comparative Example 6: The only difference between this comparative example and Example 1 is that 2 parts of biopolysaccharide and 3 parts of bioactive peptide are not added, and the rest is consistent with Example 1, namely: The following raw materials were weighed respectively according to weight: 25 parts of carob extract, 0.75 parts of baicalein, 0.75 parts of cedrol and 100 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide and sodium alginate in a mass ratio of 1:2:3:1).

[0061] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0062] Comparative Example 7: The only difference between this comparative example and Example 1 is that 2 parts of biopolysaccharide, 3 parts of bioactive peptides and 0.75 parts of cedar alcohol are not added, and the rest is consistent with Example 1, that is: The following raw materials were weighed respectively according to weight: 25 parts of carob extract, 0.75 parts of baicalein and 100 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide and sodium alginate in a mass ratio of 1:2:3:1).

[0063] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0064] Comparative Example 8: The only difference between this comparative example and Example 1 is that 2 parts of biopolysaccharide, 3 parts of bioactive peptide, 0.75 parts of baicalein and 0.75 parts of cedrol are not added, and the rest is consistent with Example 1, that is: The following raw materials were weighed respectively according to weight: 25 parts of carob extract and 100 parts of auxiliary materials (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide and sodium alginate in a mass ratio of 1:2:3:1).

[0065] The above raw materials are mixed evenly, dry granulated, sieved to obtain particles with a particle size between 80-100 meshes, and the pharmaceutical composition particles for improving sugar metabolism in female polycystic ovary syndrome are obtained.

[0066] Experiment 1: Efficacy test of different compositions on improving polycystic ovary syndrome in rats 1. Experimental animals: 85 SPF female 6-week-old SD rats, weighing 200±20g.

[0067] 2. Experimental method: All experimental rats were randomly divided into a blank control group of 5 and an experimental group of 80 according to their body weight, and placed in an SPF-grade animal breeding room for feeding, with adequate food and 5% glucose drinking water, and 14 hours of periodic light exposure every day.

[0068] Poretsky insulin (INS) combined with HCG was used to model the experimental group rats. Specifically, the experimental group rats were given a gradually increasing dose of the intermediate-acting insulin Novolin from the 1st to the 11th day of the experiment, gradually increasing from the initial 0.5IU / d to 6.0IU / d, with an increase gradient of 0.5IU / d. From the 12th to the 24th day, a fixed dose of 6.0IU / d was given, and HCG (human chorionic gonadotropin) 6.0IU / d was added. HCG was injected twice, each injection dose was 3.0IU, and the control group was injected with the same dose of normal saline as a blank control. After modeling, vaginal epithelial cell smears were performed for two cycles (5 days each cycle), and vaginal keratinized cells continued to appear, indicating that the modeling was successful.

[0069] After the model was successfully established, the rats in the test group were divided into 15 groups, 5 rats in each group, namely the model control group, experimental groups 1 to 13 and the positive control group. The experimental groups 1 to 5 were given the compositions of Examples 1 to 5, and the experimental groups 6 to 13 were given the compositions of Comparative Examples 1 to 8, respectively, at a dose of 100 mg / kg.bw. The blank control group and the model control group were gavaged with purified water, and the positive control group: diethylstilbestrol 0.5 mg / kg.bw was gavaged for 15 days.

[0070] i. Hormone level detection After the last administration, the rats in each group were fasted for 12 hours, but not water. The levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), testosterone (T), sex hormone binding globulin (SHBG), and anti-Mullerian hormone (AMH) in the rats in each group were detected by enzyme-linked immunosorbent assay (ELISA). The results are shown in Table 1.

[0071] ii. Glucose tolerance test: After fasting in the afternoon of the fourth week of modeling, blood was collected from the rat tail vein at 8:00 the next morning to measure fasting blood glucose (FPG). Glucose tolerance test was performed by intraperitoneal injection of 50% glucose injection (2g / kg). Blood was collected from the rat tail to measure blood glucose levels at 0, 15, 30, 60, and 120 minutes after injection. At the same time, EXCEL was used to analyze and compare the area under the curve (AUC). The results are shown in Table 2.

[0072] iii. Insulin resistance index (HOMA-IR) detection: The fasting insulin (FINS) was detected by ELISA method. The HOMA-IR value of each group of rats was calculated according to the formula HOMA-IR=FPG (mmol / L)×FINS (mIU / L) / 22.5. The results are shown in Table 2.

[0073] Table 1 Hormone levels of rats in each group Group FSH (IU / L) LH (ng / L) P (μg / L) T (nmol / L) SHBG (nmol / L) AMH (pg / mL) Blank Group 1.895±0.182 3.851±0.242 1.729±0.296 6.572±0.358 55.672±6.141 159.267±5.214 Model Group <![CDATA[1.514±0.273 a ]]> <![CDATA[4.829±0.341 b ]]> <![CDATA[1.389±0.242 c ]]> <![CDATA[8.753±0.425 b ]]> <![CDATA[24.196±5.422 cd ]]> <![CDATA[288.664±7.125 bc ]]> Positive group <![CDATA[2.523±0.461 c ]]> <![CDATA[3.045±0.487 c ]]> <![CDATA[6.804±0.527 ab ]]> <![CDATA[7.021±0.543 a ]]> <![CDATA[47.059±4.274 a ]]> <![CDATA[175.515±2.493 a ]]> Example 1 <![CDATA[2.057±0.523 b ]]> <![CDATA[3.554±0.411 a ]]> <![CDATA[2.012±0.624 d ]]> <![CDATA[7.358±0.244 ac ]]> <![CDATA[45.675±4.425 c ]]> <![CDATA[179.563±6.326 bc ]]> Example 2 <![CDATA[2.036±0.451 a ]]> <![CDATA[3.601±0.353 ac ]]> <![CDATA[1.989±0.547 b ]]> <![CDATA[7.324±0.511 c ]]> <![CDATA[46.011±2.976 d ]]> <![CDATA[182.582±5.438 d ]]> Example 3 <![CDATA[2.199±0.375 ac ]]> <![CDATA[3.668±0.451 d ]]> <![CDATA[2.141±0.413 a ]]> <![CDATA[7.298±0.482 d ]]> <![CDATA[45.205±3.122 c ]]> <![CDATA[183.667±4.59 d ]]> Example 4 <![CDATA[2.025±0.254 ab ]]> <![CDATA[3.756±0.385 ab ]]> <![CDATA[1.848±0.352 c ]]> <![CDATA[7.125±0.543 c ]]> <![CDATA[46.593±4.324 d ]]> <![CDATA[177.349±4.621 c ]]> Example 5 <![CDATA[1.956±0.362 ad ]]> 3.802±0.413 <![CDATA[1.819±0.525 b ]]> <![CDATA[7.096±0.457 c ]]> <![CDATA[47.142±3.685 bc ]]> <![CDATA[176.565±3.985 c ]]> Comparative Example 1 <![CDATA[1.583±0.321 d ]]> <![CDATA[4.422±0.275 c ]]> <![CDATA[1.502±0.254 d ]]> <![CDATA[8.213±0.412 d ]]> <![CDATA[33.066±3.674 ab ]]> <![CDATA[248.961±5.287 bc ]]> Comparative Example 2 <![CDATA[1.755±0.433 bc ]]> 3.823±0.359 <![CDATA[1.818±0.413 b ]]> <![CDATA[7.582±0.358 bc ]]> <![CDATA[41.577±5.342 ad ]]> <![CDATA[198.694±6.055 ab ]]> Comparative Example 3 <![CDATA[1.883±0.411 cd ]]> <![CDATA[3.591±0.283 a ]]> <![CDATA[1.953±0.402 bc ]]> <![CDATA[7.423±0.341 d ]]> <![CDATA[45.041±5.103 c ]]> <![CDATA[182.422±5.251 ad ]]> Comparative Example 4 <![CDATA[1.891±0.364 cd ]]> <![CDATA[3.602±0.303 a ]]> <![CDATA[1.974±0.391 c ]]> <![CDATA[7.431±0.259 d ]]> <![CDATA[44.425±3.952 ab ]]> <![CDATA[182.854±2.984 ad ]]> Comparative Example 5 <![CDATA[1.728±0.441 a ]]> <![CDATA[4.172±0.421 ac ]]> <![CDATA[1.722±0.405 a ]]> <![CDATA[7.882±0.427 bc ]]> <![CDATA[38.564±4.825 ac ]]> <![CDATA[216.244±5.110 b ]]> Comparative Example 6 <![CDATA[1.659±0.297 b ]]> <![CDATA[4.314±0.342 ab ]]> <![CDATA[1.603±0.325 ab ]]> <![CDATA[8.127±0.364 c ]]> <![CDATA[34.593±3.645 ad ]]> <![CDATA[230.154±4.183 bd ]]> Comparative Example 7 <![CDATA[1.628±0.346 b ]]> <![CDATA[4.409±0.547 c ]]> <![CDATA[1.511±0.287 d ]]> <![CDATA[8.139±0.515 c ]]> <![CDATA[33.369±3.986 bc ]]> <![CDATA[241.536±3.965 cd ]]> Comparative Example 8 <![CDATA[1.579±0.215 d ]]> <![CDATA[4.476±0.623 d ]]> <![CDATA[1.498±0.388 c ]]> <![CDATA[8.255±0.476 ad ]]> <![CDATA[32.884±4.363 b ]]> <![CDATA[252.843±4.557 ac ]]> Note: Different letters in the same column indicate statistical differences between the corresponding groups, P < 0.05.

[0074] Table 2 Effects of different compositions on glucose tolerance and insulin resistance in rats Group FPG (mmol / L) AUC (min·mmol / L) HOMA-IR Blank Group 3.493±0.234 1219.514±84.369 3.612±0.294 Model Group <![CDATA[4.461±0.257 a ]]> <![CDATA[2084.467±113.243 b ]]> <![CDATA[12.462±0.367 c ]]> Positive group <![CDATA[2.895±0.411 d ]]> <![CDATA[1632.423±120.564 c ]]> <![CDATA[8.121±0.286 d ]]> Example 1 <![CDATA[3.652±0.542 bc ]]> <![CDATA[1309.282±104.367 b ]]> <![CDATA[6.554±0.695 c ]]> Example 2 <![CDATA[3.694±0.621 c ]]> <![CDATA[1325.154±125.143 b ]]> <![CDATA[6.601±0.517 b ]]> Example 3 <![CDATA[3.679±0.549 d ]]> <![CDATA[1316.533±130.421 c ]]> <![CDATA[6.583±0.451 b ]]> Example 4 <![CDATA[3.542±0.473 ab ]]> <![CDATA[1286.592±115.387 bc ]]> <![CDATA[6.501±1.002 bc ]]> Example 5 <![CDATA[3.529±0.527 ad ]]> <![CDATA[1279.439±98.352 bc ]]> <![CDATA[6.463±0.674 c ]]> Comparative Example 1 <![CDATA[4.196±0.533 bd ]]> <![CDATA[1909.365±89.287 ac ]]> <![CDATA[10.163±0.557 bc ]]> Comparative Example 2 <![CDATA[3.837±0.359 ac ]]> <![CDATA[1643.294±106.276 bd ]]> <![CDATA[9.272±0.764 cd ]]> Comparative Example 3 <![CDATA[3.705±0.522 d ]]> <![CDATA[1392.572±97.349 bc ]]> <![CDATA[7.699±0.733 ab ]]> Comparative Example 4 <![CDATA[3.693±0.547 c ]]> <![CDATA[1368.524±115.482 d ]]> <![CDATA[7.637±0.825 ab ]]> Comparative Example 5 <![CDATA[3.925±0.289 d ]]> <![CDATA[1795.257±92.349 ac ]]> <![CDATA[9.534±0.552 bd ]]> Comparative Example 6 <![CDATA[4.083±0.336 bc ]]> <![CDATA[1890.228±113.572 cd ]]> <![CDATA[9.997±0.521 ad ]]> Comparative Example 7 <![CDATA[4.176±0.422 ad ]]> <![CDATA[1896.267±96.346 cd ]]> <![CDATA[10.034±0.452 bc ]]> Comparative Example 8 <![CDATA[4.251±0.367 cd ]]> <![CDATA[1928.548±101.248 ad ]]> <![CDATA[10.258±0.803 cd ]]> Note: Different letters in the same column indicate statistical differences between the corresponding groups, P < 0.05.

[0075] From the results in Table 1 above, it can be seen that, compared with Comparative Examples 1-8, the compositions of Examples 1-5 of the present invention can significantly improve the hormone levels of rats with polycystic ovary syndrome, making them closer to normal levels, and the effects of Examples 4 and 5 are more obvious. From the results in Table 2 above, it can be seen that, compared with Example 1, the glucose tolerance and insulin resistance index of rats in Examples 4 and 5 groups are closer to the normal values ​​of the blank group, and the glucose tolerance and insulin resistance index of rats in Comparative Examples 1-8 groups are significantly worse than those in Example 1 group.

[0076] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment as above, it is not used to limit the present invention. Any technician familiar with this profession can make some changes or modifications to equivalent embodiments of equivalent changes by using the methods and technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome, characterized in that: The pharmaceutical composition comprises carob extract, baicalein, cedrol, bioactive peptides, biopolysaccharides and auxiliary materials.

2. The pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome according to claim 1, characterized in that: In terms of weight, the pharmaceutical composition comprises: 20-30 parts of carob extract, 1-3 parts of biopolysaccharide, 0.5-1 part of baicalein, 0.5-1 part of cedrol, 0.1-0.5 part of bioactive peptide and 80-120 parts of auxiliary materials.

3. The pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome according to claim 1 or 2, characterized in that: The mass content of D-chiro-inositol in the carob extract is ≥95%.

4. The pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome according to claim 1 or 2, characterized in that: The biological polysaccharide is selected from one or a mixture of two or more of wolfberry polysaccharide, tremella polysaccharide, macroalgae polysaccharide, lemon peel polysaccharide, blackberry polysaccharide and honeysuckle leaf polysaccharide.

5. The pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome according to claim 1 or 2, characterized in that: The bioactive peptide is selected from one or a mixture of two or more of leech active peptides, abalone active peptides, milk-derived active peptides, and silkworm pupa-derived active peptides.

6. The pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome according to claim 1 or 2, characterized in that: The milk-derived active peptide is selected from any one of horse milk-derived active peptides, bovine milk-derived active peptides, and goat milk-derived active peptides, or a mixture of two or more thereof.

7. The pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome according to claim 1 or 2, characterized in that: The auxiliary material is selected from one or a mixture of two or more of a diluent, a flavoring agent, a lubricant, a glidant, a disintegrant, and a binder.

8. The pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome according to claim 7, characterized in that: The diluent is selected from one or a mixture of two or more of pregelatinized starch, mannitol, calcium hydrogen phosphate, microcrystalline cellulose, and xylitol; The flavoring agent is selected from one or a mixture of two or more of mint powder flavor, lemon powder flavor, strawberry powder flavor, cream powder flavor, and banana powder flavor; The lubricant is selected from one or a mixture of two or more of magnesium stearate, micro-powder silica gel, calcium silicate, and talc; The glidant is selected from silicon dioxide; The disintegrant is selected from one or a mixture of two or more of dry starch, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, and polyvinyl pyrrolidone; The adhesive is selected from starch slurry, polyvidone, gelatin, gum arabic, sodium alginate, polyethylene glycol, or a mixture of two or more thereof.

9. The pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome according to claim 1 or 2, characterized in that: The pharmaceutical composition is in the form of tablets, capsules, pills, mixtures, gels, ointments, granules, powders, pastes, granules, pills, oral liquids, pills, injections or injections.

10. Use of the pharmaceutical composition for improving glucose metabolism in female polycystic ovary syndrome according to claim 1 or 2 in the preparation of a medicament for improving and / or treating glucose metabolism in female polycystic ovary syndrome.