Application of carob extract in improving glucose metabolism in women with polycystic ovary syndrome

Abstract

The present invention belongs to the technical field of plant extracts, and more specifically, relates to the use of a carob extract in a drug for improving glucose metabolism / polycystic ovary syndrome in women. The present invention discloses a pharmaceutical composition for improving glucose metabolism and treating polycystic ovary syndrome in women, the pharmaceutical composition comprising: carob extract, baicalein, cedrol, a bioactive peptide, a biopolysaccharide, and excipients. The composition of the present invention has the effects of lowering blood sugar and blood lipids, improving insulin function, and also has antioxidant and immunity-enhancing effects. By combining the above substances, a synergistic effect is achieved, further enhancing the effect of improving / treating polycystic ovary syndrome in women associated with abnormal glucose metabolism.

Description

Technical Field

[0001] The present 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 beans, are found along the Mediterranean coast and in California, primarily cultivated in Guangxi, Sichuan, Yunnan, and Guangdong. Containing natural polysaccharides, vitamins, proteins, and trace elements, carob has high nutritional and medicinal value, making it suitable for long-term consumption by those with stomach and heart problems. It is also effective in preventing colds and coughs. Carob extract is obtained by solvent extraction and vacuum concentration. Carob extract is a light green liquid that is readily soluble in water and ethanol. It can be used as a dietary supplement, primarily to regulate hormone balance, improve metabolic syndrome, alleviate polycystic ovary syndrome, and lower blood sugar.

[0003] Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive and metabolic disorders in women, causing multiple health issues, including endocrine disorders, glucose and lipid metabolism, reproductive health, and mental health. The main clinical features of PCOS are menstrual irregularities, hyperandrogenism, and polycystic ovarian changes, often accompanied by obesity and insulin resistance. It is the most common cause of menstrual irregularities in women of childbearing age and the leading cause of anovulatory infertility. In addition to causing symptoms such as decreased fertility and obesity in women of childbearing age, PCOS also has significant metabolic effects. If not promptly corrected, it can 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 a use of a carob bean extract in a drug for improving sugar metabolism / polycystic ovary syndrome in women. By combining the carob bean extract with a variety of substances, the effect of the carob bean 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 glucose 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 biopolysaccharide, 0.5-1 part of baicalein, 0.5-1 part of cedarol, 0.1-0.5 part of bioactive peptide 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 leaf 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, micropowder 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:

[0021] The raw materials are weighed according to the ratio and mixed evenly, and then prepared into a suitable form as required to obtain a pharmaceutical composition for improving sugar metabolism in female polycystic ovary syndrome.

[0022] Another aspect of the present invention provides a use of the pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome as described above in the preparation of a drug for improving and / or treating glucose metabolism in women with polycystic ovary syndrome.

[0023] By means of the above technical solution, the present invention has at least the following advantages:

[0024] 1. The present invention uses carob extract, baicalein, cedrol, bioactive peptides, and biopolysaccharides as main active substances. Through the rational combination of these substances and the action of excipients, a composition is obtained. The composition can effectively improve the insulin activity of polycystic ovary syndrome, regulate endocrine function, and improve hormonal balance, thereby regularizing menstruation and ovulation in patients, returning hormones to normal levels, improving fertility, and reducing the risk of diseases such as diabetes, cardiovascular disease, and endometrial cancer. In other words, it has a significant effect on improving or treating polycystic ovary syndrome in women with poor glucose metabolism.

[0025] 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. Each of the above substances has the effects of lowering blood sugar, lowering blood lipids, and improving insulin function, and also has antioxidant and immunity-enhancing effects. By combining the above substances with carob extract, baicalein, and cedrol, a synergistic effect is achieved, further improving the effect of improving / treating female polycystic ovary syndrome associated with abnormal glucose metabolism.

[0026] 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 following is a detailed description of the preferred embodiments of the present invention. DETAILED DESCRIPTION

[0027] In order to make the technical means, creative features, objectives and effects achieved by the present invention easier to understand, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction 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 making creative efforts shall fall within the scope of protection of the present invention.

[0028] Carob extract is obtained from carob beans through solvent extraction and reduced-pressure concentration. Carob extract is a light green liquid that is readily soluble in water and ethanol. It can be used as a dietary supplement. Its primary functions include regulating hormone balance, improving metabolic syndrome, improving polycystic ovary syndrome, and lowering blood sugar. The main active ingredient in carob extract is D-chiro-inositol. D-chiro-inositol (DCI) is the optically active isomer of the nine inositol isomers. Recent research has shown that, in addition to its ability to promote hepatic lipid metabolism, D-chiro-inositol (DCI) also exhibits insulin sensitization, blood sugar reduction, improved ovulation in patients with polycystic ovary syndrome (PCOS), hormone regulation, and menstrual irregularities. It also has unique physiological functions such as antioxidant, anti-aging, and anti-inflammatory properties. Unless otherwise specified, the carob extract described herein was purchased from Shandong Aimi Biotechnology Co., Ltd., and the D-chiro-inositol content was ≥95%.

[0029] Baicalein, one of the most abundant flavonoids in Scutellaria baicalensis, has multiple benefits, including reducing cerebral vascular resistance, improving cerebral circulation, increasing cerebral blood flow, and inhibiting platelet aggregation. It is clinically used to treat paralysis following cerebrovascular disease. Furthermore, Scutellaria baicalensis has a broad antibacterial spectrum, inhibiting Shigella dysenteriae, Corynebacterium diphtheriae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, and meningococci. Unless otherwise specified, the baicalein described herein was purchased from Yunnan Siji Biological Co., Ltd.

[0030] Extracted from Atlantic cedar, cedarwood is a natural sesquiterpene alcohol with diverse pharmacological activities. Studies on cedarwood isolated from the essential oil of Nitraria serrata have shown significant inhibitory activity against Staphylococcus aureus, Bacillus subtilis, and Salmonella typhimurium. Several other studies have also demonstrated its potential for cancer treatment. For example, cedarwood can induce cell cycle arrest and enhance apoptosis in colorectal cancer cells, making it considered an effective treatment for colorectal cancer. It can also inhibit the growth of glioblastoma tumors and induce intracellular DNA damage, thereby inhibiting their progression. Furthermore, studies have shown that cedarwood inhibits dihydrotestosterone (DHT)-induced androgen receptor (AR) activation in cultured fetal mouse dermal fibroblasts, suggesting that cedarwood has a modulating effect on androgen levels. Unless otherwise specified, the cedarwood (purity >98%) described herein was purchased from Shanghai TCI Chemical Industry Development Co., Ltd.

[0031] Bioactive peptides (BAPs) are peptide sequences with specific biological activities. Depending on their source, BAPs can be divided into exogenous and endogenous BAPs. Exogenous BAPs refer to BAPs outside the human body, namely, those naturally present in animals, plants, and microorganisms, as well as those produced through the degradation of animal and plant proteins. Endogenous BAPs are those produced through enzymatic hydrolysis within the human body and present in the body. These include hormone peptides such as insulin and adrenocorticotropic hormone, and neuropeptides such as endorphins and enkephalins. Based on their different effects on the body, BAPs can be broadly categorized 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-enhancing peptides, and antifungal peptides. These BAPs play an important role in maintaining and restoring health. Dairy-derived BAPs are primarily derived from casein and whey protein. Casein itself lacks an active milk protein structure and can be produced through hydrolysis of protein or peptide hydrolysates, fermentation, and gastrointestinal digestion. Research has shown that BAPs possess a wide range of biological functions, including antioxidant, antihypertensive, antihyperglycemic, antibacterial, immunomodulatory, and anti-inflammatory properties. Due to their high specificity, low toxicity, high structural diversity, and low molecular weight, they are considered ideal for use in health supplements or functional foods.

[0032] In one aspect, the bioactive peptides used in the present invention can be active peptides derived from horse milk, bovine milk, or goat milk. Unless otherwise specified, the preparation method of the horse milk-derived active peptides described in the examples is based on the content described in CN115028706A, which is incorporated herein by reference. The specific process is as follows: fresh horse milk is centrifuged at 4°C and 10,000g for 5 minutes to defatted to obtain skimmed horse milk. The skimmed horse milk is adjusted to pH 4.2 with HCl in a 45°C water bath, centrifuged at 10,000g for 5 minutes, and the precipitate is freeze-dried using a freeze dryer to obtain freeze-dried horse milk casein powder. Freeze-dried horse milk casein 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 suspension (Kazachstania unispora KU530, Lactobacillus helveticus (ATCC: 55163), and Lactobacillus paracasei (Jiangsu Zishi Weikang Biotechnology Co., Ltd.) to a viable count of 1 × 10 8 CFU / mL) was inoculated into a freeze-dried mare's milk casein solution at a 5% volume fraction for fermentation. Fermentation was performed at 35°C, a shaker speed of 200 rpm, and a fermentation time of 72 hours to obtain a fermentation broth. The pH of the resulting fermentation broth was adjusted to 8, and 8% by weight trypsin (1200 U / mg) was added. The mixture was reacted at 37°C for 6 hours to obtain a fermentation hydrolyzate. This solution was then filtered through an ultrafiltration membrane with a 1 kDa cutoff to obtain a solution containing fractions with a molecular weight ≤1 kDa. Finally, the solution was freeze-dried and the lyophilized powder was collected, which is the mare's milk-derived active peptide. This active peptide has a low molecular weight of less than 1 kDa and low immunogenicity, making it highly suitable for human use. Unless otherwise specified, bovine and goat milk-derived active peptides were prepared using the same method and are not described here.

[0033] 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 by-products 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. They 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 activities, can be digested and absorbed in the gastrointestinal tract through food matrices, and exert beneficial functions. Unless otherwise specified, the preparation method of the silkworm pupa-derived active peptides described in the embodiments of the present invention is: fresh silkworm pupae are dried and crushed and then passed 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. The resulting dispersion was then adjusted to pH 10 with sodium hydroxide, and 5% by weight of alkaline protease (enzyme activity 200 U / mg) and 5% by weight of trypsin (1200 U / mg) were added. The mixture was reacted at 50°C for 2 hours to obtain an enzymatic hydrolyzate. The solution was then filtered through an ultrafiltration membrane with a cutoff of 1 kDa to obtain a solution containing components with a molecular weight of ≤1 kDa. Finally, the solution was freeze-dried and the lyophilized powder was collected, which was the silkworm pupa-derived active peptide.

[0034] 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. Leech, as a traditional Chinese medicine for promoting blood circulation and removing blood stasis, has the functions of breaking blood, removing blood stasis, and promoting menstruation. Leech active polypeptide drugs are relatively commonly used natural thrombin-specific inhibitors with good anticoagulant and anti-arteriovenous thrombotic effects and low toxic and side effects. Unless otherwise specified, the preparation methods of the abalone bioactive peptides and leech active polypeptides described in the present invention are consistent with those of the silkworm pupa-derived active peptides and will not be repeated here.

[0035] 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.

[0036] Unless otherwise specified, the preparation process of 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.

[0037] 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.

[0038] Unless otherwise specified, percentage concentrations referred to in the present invention refer to final concentrations, which refer to the percentage of an added component in the system after the addition of the component.

[0039] The temperature parameters in the present invention, unless otherwise specified, allow for either constant temperature treatment or treatment within a certain temperature range. The constant temperature treatment allows for temperature fluctuations within the precision range controlled by the instrument.

[0040] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0041] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0042] Example 1:

[0043] The following raw materials were weighed out according to weight: 25 parts of carob extract, 2 parts of biopolysaccharide (a mixture of wolfberry polysaccharide, tremella polysaccharide, macroalgae polysaccharide, lemon peel polysaccharide, blackberry polysaccharide, and honeysuckle polysaccharide in equal mass ratio), 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 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).

[0044] The above raw materials are mixed evenly, dry granulated, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0045] Example 2:

[0046] The following raw materials were weighed out according to weight: 20 parts of carob extract, 3 parts of biopolysaccharides (a mixture of wolfberry polysaccharide, tremella polysaccharide, macroalgae polysaccharide, lemon peel polysaccharide, blackberry polysaccharide, and honeysuckle leaf polysaccharide in equal mass ratios), 0.5 parts of baicalein, 0.5 parts of cedarol, 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 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, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0048] Example 3:

[0049] 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 ratios), 1 part of baicalein, 1 part of cedarol, 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 ratios), and 120 parts of excipients (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0050] The above raw materials are mixed evenly, dry granulated, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0051] Example 4:

[0052] The following raw materials were weighed out in parts by weight: 25 parts of carob extract, 2 parts of biopolysaccharide (a mixture of wolfberry polysaccharide, tremella polysaccharide, macroalgae polysaccharide, lemon peel polysaccharide, blackberry polysaccharide, and honeysuckle polysaccharide in an equal mass ratio of 1:1:2:2:1:1), 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 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).

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

[0054] Example 5:

[0055] The following raw materials were weighed out in parts by weight: 25 parts of carob extract, 2 parts of biopolysaccharide (a mixture of wolfberry polysaccharide, tremella polysaccharide, macroalgae polysaccharide, lemon peel polysaccharide, blackberry polysaccharide, and honeysuckle polysaccharide in equal mass ratios), 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 of 1:1:0.5:2), 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).

[0056] The above raw materials are mixed evenly, dry granulated, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0057] Comparative Example 1:

[0058] 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:

[0059] The following raw materials were weighed in parts by 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 ratios), 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 excipients (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0060] The above raw materials are mixed evenly, dry granulated, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0061] Comparative Example 2:

[0062] The only difference between this comparative example and Example 1 is that 2 parts of biopolysaccharide are not added, and the rest are consistent with Example 1, namely:

[0063] 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 excipients (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0064] The above raw materials are mixed evenly, dry granulated, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0065] Comparative Example 3:

[0066] 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, namely:

[0067] The following raw materials were weighed out according to weight: 25 parts of carob extract, 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 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 excipients (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0068] The above raw materials are mixed evenly, dry granulated, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0069] Comparative Example 4:

[0070] The only difference between this comparative example and Example 1 is that 0.75 parts of cedarol is not added, and the rest is consistent with Example 1, namely:

[0071] The following raw materials were weighed out according to weight: 25 parts of carob extract, 2 parts of biopolysaccharide (a mixture of wolfberry polysaccharide, tremella polysaccharide, macroalgae polysaccharide, lemon peel polysaccharide, blackberry polysaccharide, and honeysuckle polysaccharide 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 excipients (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0072] The above raw materials are mixed evenly, dry granulated, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0073] Comparative Example 5:

[0074] The only difference between this comparative example and Example 1 is that 3 parts of bioactive peptides were not added, and the rest were consistent with Example 1, namely:

[0075] The following raw materials were weighed in parts by weight: 25 parts of carob extract, 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 ratios), 0.75 parts of baicalein, 0.75 parts of cedarol, 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).

[0076] The above raw materials are mixed evenly, dry granulated, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0077] Comparative Example 6:

[0078] 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:

[0079] The following raw materials were weighed respectively in parts by weight: 25 parts of carob extract, 0.75 parts of baicalein, 0.75 parts of cedarol, and 100 parts of an auxiliary material (a mixture of microcrystalline cellulose, magnesium stearate, silicon dioxide, and sodium alginate in a mass ratio of 1:2:3:1).

[0080] The above raw materials are mixed evenly, dry granulated, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0081] Comparative Example 7:

[0082] The only difference between this comparative example and Example 1 is that 2 parts of biopolysaccharide, 3 parts of bioactive peptide and 0.75 parts of cedarol are not added, and the rest is consistent with Example 1, namely:

[0083] The following raw materials were weighed respectively in parts by weight: 25 parts of carob extract, 0.75 parts of baicalein, 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).

[0084] The above raw materials are mixed evenly, dry granulated, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0085] Comparative Example 8:

[0086] 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 cedarol are not added, and the rest is consistent with Example 1, that is:

[0087] The following raw materials were weighed respectively in parts by 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).

[0088] The above raw materials are mixed evenly, dry granulated, and sieved to obtain particles with a particle size between 80 and 100 meshes, thereby obtaining the pharmaceutical composition particles for improving sugar metabolism in women with polycystic ovary syndrome.

[0089] Experiment 1: Efficacy test of different compositions on improving polycystic ovary syndrome in rats

[0090] 1. Experimental animals: 85 SPF female 6-week-old SD rats, weighing 200±20 g.

[0091] 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. The rats were placed in an SPF animal breeding room and fed with sufficient food and 5% glucose drinking water, and given 14 hours of periodic light every day.

[0092] The Poretsky insulin (INS) combined with human chorionic gonadotropin (HCG) was used to establish a model in rats. Specifically, from days 1 to 11 of the experiment, rats in the experimental group were given increasing doses of the intermediate-acting insulin Novolin, starting at 0.5 IU / d and gradually increasing to 6.0 IU / d, with a gradient of 0.5 IU / d. From days 12 to 24, a fixed dose of 6.0 IU / d was administered, along with 6.0 IU / d of human chorionic gonadotropin (HCG). HCG was administered in two injections, each at a dose of 3.0 IU. The control group received the same dose of saline as a blank control. After modeling, vaginal epithelial cell smears were performed for two consecutive cycles (5 days each), and vaginal keratinized cells continued to appear, indicating successful modeling.

[0093] After successful modeling, the rats in the test group were divided into 15 groups, with 5 rats in each group, namely the model control group, experimental groups 1 to 13 and the positive control group. Experimental groups 1 to 5 were given the compositions of Examples 1 to 5, and 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.

[0094] 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.

[0095] ii. Glucose tolerance test: After fasting in the afternoon of the fourth week of modeling, blood was collected from the tail vein of the mice at 8:00 a.m. the following morning for fasting blood glucose (FPG) measurement. Glucose tolerance was tested by intraperitoneal injection of 50% glucose (2 g / kg). Blood glucose levels were measured at 0, 15, 30, 60, and 120 minutes after injection. The area under the curve (AUC) was analyzed and compared using Excel. The results are shown in Table 2.

[0096] iii. Insulin resistance index (HOMA-IR) detection: Fasting insulin (FINS) was detected by ELISA. 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.

[0097] Table 1 Hormone levels of rats in each group

[0098] 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 ]]>

[0099] Note: Different letters in the same column indicate statistical differences between the corresponding groups, P < 0.05.

[0100] Table 2 Effects of different compositions on glucose tolerance and insulin resistance in rats

[0101] 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 ]]>

[0102] Note: Different letters in the same column indicate statistical differences between the corresponding groups, P < 0.05.

[0103] As can be seen from the results in Table 1 above, 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. As can be seen from the results in Table 2 above, 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.

[0104] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as a preferred embodiment as above, it is not intended to limit the present invention. Any technician familiar with this profession can make slight changes or modifications to equivalent embodiments of the methods and technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still 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, by weight, 20-30 parts of carob extract, 1-3 parts of biopolysaccharide, 0.5-1 part of baicalein, 0.5-1 part of cedarol, 0.1-0.5 part of bioactive peptide, and 80-120 parts of excipients. The biopolysaccharide is a mixture of wolfberry polysaccharide, tremella polysaccharide, macroalgae polysaccharide, lemon peel polysaccharide, blackberry polysaccharide and honeysuckle leaf polysaccharide in equal mass ratios; The bioactive peptide is a mixture of leech active peptide, abalone active peptide, horse milk-derived active peptide, and silkworm chrysalis-derived active peptide in equal mass ratios; or, the bioactive peptide is a mixture of leech active peptide, abalone active peptide, goat milk-derived active peptide, and silkworm chrysalis-derived active peptide in equal mass ratios; or, the bioactive peptide is a mixture of leech active peptide, abalone active peptide, bovine milk-derived active peptide, and silkworm chrysalis-derived active peptide in equal mass ratios; The excipient 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; The mass content of D-chiro-inositol in the carob extract is ≥95%.

2. The pharmaceutical composition for improving glucose metabolism in women with polycystic ovary syndrome according to claim 1, 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; And / or, 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; And / or, the lubricant is selected from one or a mixture of two or more of magnesium stearate, micropowder silica gel, calcium silicate, and talc; and / or, the glidant is selected from silicon dioxide; and / or, the disintegrant is selected from one or a mixture of two or more of dry starch, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, and polyvinyl pyrrolidone; And / or, 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.

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

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