Oral food composition for female breast volume enhancement and gynecomastia improvement, beauty enhancement through estrogen / progesterone balance regulation and collagen synthesis promotion and manufacturing method thereof

Abstract

The present invention relates to an orally ingestible food composition for improving female breast volume and gynecomastia and improving beauty through the regulation of estrogen / progesterone balance and the promotion of collagen synthesis, and a method for manufacturing the same. Specifically, the invention relates to a food composition prepared using 3-7 parts by weight of Cynanchum wilfordii Hemsley extract powder, 50-65 parts by weight of pomegranate concentrate powder, 8-12 parts by weight of Sophora japonica fruit extract powder, 8-12 parts by weight of soybean extract powder, 3-7 parts by weight of bromelain powder, 3-7 parts by weight of crystalline cellulose 102, 0.2-0.5 parts by weight of vitamin B1 (hydrochloride), 0.2-0.4 parts by weight of vitamin B2, 0.3-0.5 parts by weight of vitamin B6 hydrochloride, and 0.3-0.6 parts by weight of vitamin B12. The manufacturing method of the present invention comprises a raw material preparation step for standardizing the active ingredients of each raw material, a plant extract mixture preparation step, a functional mixture preparation step, a vitamin complex preparation step, a final composition preparation step, and a step of forming into an orally ingestible form.

Description

Technology Field

[0001] The following examples relate to an oral food composition for improving female breast volume and gynecomastia, and improving beauty through the regulation of estrogen / progesterone balance and the promotion of collagen synthesis, and a method for manufacturing the same. Background Technology

[0002] With the increasing interest in beauty and health among modern women, there is a continuously rising demand for natural breast volume improvement and gynecomastia relief through hormone balance regulation. In particular, an imbalance between the female hormones estrogen and progesterone is known to negatively affect the development of breast tissue, reduce collagen synthesis, and overall beauty and health of women.

[0003] While conventional hormone replacement therapy (HRT) is effective in treating menopausal symptoms, concerns regarding its safety have been raised following the Women's Health Initiative report that it increases the risk of breast cancer, heart disease, and stroke by 26%, 29%, and 41%, respectively. Consequently, there is growing interest in safe, natural alternative therapies with fewer side effects.

[0004] Cynanchum wilfordii Hemsley is a traditional herbal material recorded in the *Donguibogam* that possesses anti-inflammatory, antioxidant, and anticancer effects. In particular, it is being studied for its ability to improve women's health without side effects on estrogen receptors. However, existing studies have been limited to verifying the effects of single components, and there is a lack of systematic research on synergistic effects and manufacturing methods through complex formulations.

[0005] In addition, there is a need to develop an oral food composition that effectively combines functional ingredients such as bromelain to promote collagen synthesis, soybean extract rich in isoflavones, and pomegranate concentrate powder with excellent antioxidant effects, thereby regulating the estrogen / progesterone balance while simultaneously improving breast volume and gynecomastia. Prior art literature

[0006] Korean Published Patent 10-2020-0016448 Korean Registered Patent 10-2497345 Korean Registered Patent 10-1754227 Korean Registered Patent 10-2111752 The problem to be solved

[0007] The present invention provides a food composition based on natural materials that can safely regulate the estrogen / progesterone balance without adverse effects on estrogen receptors.

[0008] In addition, the present invention develops an optimized formulation using Cynanchum wilfordii Hemsley extract powder as the main ingredient to promote collagen synthesis and exhibit an effect of enhancing female breast volume.

[0009] In addition, the present invention establishes a step-by-step manufacturing process capable of maximizing the synergistic effects of functional ingredients such as pomegranate concentrate powder, Sophora japonica fruit extract powder, soybean extract powder, and bromelain powder.

[0010] In addition, the present invention provides a systematic manufacturing method capable of producing products of consistent quality by standardizing the content of active ingredients of each raw material and ensuring stability.

[0011] In addition, the present invention develops a food composition that can be manufactured in various formulations such as tablets, capsules, and granules and has excellent bioavailability when ingested orally.

[0012] In addition, the present invention provides a composition for regulating hormone balance that can be effectively applied to the improvement of gynecomastia in men.

[0013] In addition, the present invention provides a safe alternative therapy that can maximize cosmetic improvement effects while minimizing the side effects of existing hormone replacement therapy. means of solving the problem

[0014] The present invention relates to a method for preparing an orally ingestible food composition for improving female breast volume, improving gynecomastia, and improving beauty by regulating estrogen / progesterone balance and promoting collagen synthesis, comprising 3-7 parts by weight of Cynanchum wilfordii Hemsley extract powder, 50-65 parts by weight of pomegranate concentrate powder, 8-12 parts by weight of Sophora japonica fruit extract powder, 8-12 parts by weight of soybean extract powder, 3-7 parts by weight of bromelain powder, 3-7 parts by weight of crystalline cellulose 102, 0.2-0.5 parts by weight of vitamin B1 (hydrochloride), 0.2-0.4 parts by weight of vitamin B2, 0.3-0.5 parts by weight of vitamin B6 hydrochloride, and 0.3-0.6 parts by weight of vitamin B12.

[0015] At this time, (a) a step of preparing raw materials comprising 3-7 parts by weight of Cynanchum wilfordii Hemsley extract powder, 50-65 parts by weight of pomegranate concentrate powder, 8-12 parts by weight of Sophora japonica fruit extract powder, 8-12 parts by weight of soybean extract powder, 3-7 parts by weight of bromelain powder, 3-7 parts by weight of crystalline cellulose 102, 0.2-0.5 parts by weight of vitamin B1 (hydrochloride), 0.2-0.4 parts by weight of vitamin B2, 0.3-0.5 parts by weight of vitamin B6 hydrochloride, and 0.3-0.6 parts by weight of vitamin B12; (b) a step of preparing a plant extract mixture by mixing the Cynanchum wilfordii extract powder, the Sophora japonica fruit extract powder, and the soybean extract powder; (c) a step of preparing a functional mixture by mixing the pomegranate concentrate powder and the bromelain powder; (d) a step of preparing a vitamin complex by mixing the vitamin B1 (hydrochloride), the vitamin B2, the vitamin B6 hydrochloride, and the vitamin B12; (e) a step of preparing a final composition by sequentially mixing the plant extract mixture, the functional mixture, the vitamin complex, and the crystalline cellulose 102; (f) a step of molding the final composition into a form suitable for oral intake;

[0016] At this time, step (a) is a step of standardizing the Cynanchum wilfordii extract powder to a cyanoside content of 0.2-0.4 wt%, standardizing the pomegranate concentrate powder to an ellagic acid content of 4-6 wt%, the Sophora japonica fruit extract powder to a rutin content of 8-12 wt%, and the soybean extract powder to an isoflavone content of 20-30 wt% by HPLC, adjusting the enzyme activity of the bromelain powder to 2000-3000 GDU / g, and confirming and quantifying the purity of vitamins B1, B2, B6, and B12, and step (b) is a step of pre-treating the Cynanchum wilfordii extract powder at a temperature of 25-35℃, wetting the Sophora japonica fruit extract powder with purified water, and treating the soybean extract powder with nitrogen gas for oxidation prevention, then sequentially mixing them, undergoing first and second mixing, and drying at a temperature of 40-60℃. Step (c) involves preparing a plant extract mixture by homogenizing and then aging at a temperature of 20-25℃ for 45-60 minutes; Step (c) involves pre-treating pomegranate concentrate powder at a temperature of 28-32℃ and standardizing the enzyme activity of bromelain powder to 2200-2800 GDU / g, then mixing the pomegranate concentrate powder and bromelain powder in a weight ratio of 11:1-13:1 in a V-type mixer, adding ascorbic acid as an antioxidant for enzyme stabilization treatment, and then aging in a nitrogen-substituted sealed container for 30-42 hours to prepare a functional mixture; and Step (d) involves confirming the purity of vitamins B1, B2, and B6 to be 78%, 100%, and 82% or higher, respectively, diluting vitamin B12 to 1.0% or higher, and then mixing the water-soluble vitamins in a ratio of 1:0.94±0.05:1.23±0.05 The step of preparing a vitamin complex involves first mixing by weight ratio, adding diluted vitamin B12 at a weight ratio of 1:0.16±0.02 for second mixing, sieving through a 200-300 mesh sieve, and stabilizing at 10-20℃; wherein the above step (e) involves pre-stirring crystalline cellulose 102 in a large-capacity mixer, then adding a plant extract mixture at 15-25% of the target weight of the final composition, a functional mixture at 60-70%, and a vitamin complex at 1.5-2%.The step of preparing a final composition involves sequentially adding at 5% and performing first, second, and third mixing respectively, then finally homogenizing, sifting through 150-200 mesh to adjust the moisture content to 3.0% or less, and stabilizing; and the step (f) involves preparing tablets by pressing the final composition at a compression pressure of 8-15 kN, preparing capsules by filling 500-800 mg into hard gelatin capsules, or preparing granules by using a fluid bed granulator at an inlet temperature of 60-80℃, then adjusting the particle size and moisture content of each formulation, packaging them in aluminum-PTP packaging or HDPE containers, and storing them at a temperature of 15-25℃ while maintaining quality control.

[0017] At this time, step (a) comprises: (a1) a step of standardizing the above-mentioned Cynanchum wilfordii extract powder by HPLC to a cynapaposide content of 0.2-0.4 wt% and drying it for 24-48 hours at 40-60℃ and a relative humidity of 30% or less; (a2) a step of standardizing the above-mentioned pomegranate concentrate powder by HPLC to a ellagic acid content of 4-6 wt% and storing it at a temperature of 15-25℃ and a humidity of 15% or less; (a3) ​​a step of standardizing the above-mentioned Sophora japonica fruit extract powder by HPLC to a rutin content of 8-12 wt% and grinding it to 80-120 mesh; (a4) a step of standardizing the above-mentioned soybean extract powder by HPLC to an isoflavone content of 20-30 wt% and grinding it to 80-120 mesh; (a5) adjusting the bromelain powder to an enzyme activity of 2000-3000 GDU / g by spectrophotometry and storing it under refrigeration at 2-8℃; (a6) homogenizing the crystalline cellulose 102 using a vibrator to obtain a particle size of 50-100 μm; (a7) selecting the vitamin B1 (hydrochloride) to a purity of 78% or higher and quantifying it to an amount equivalent to 1.2 mg per batch of the final product; (a8) selecting the vitamin B2 to a purity of 98% or higher and quantifying it to an amount equivalent to 1.4 mg per batch of the final product; (a9) selecting the vitamin B6 hydrochloride to a purity of 82% or higher and quantifying it to an amount equivalent to 1.5 mg per batch of the final product; (a10) A step of diluting and adjusting the vitamin B12 in the form of a premix with a purity of 1% or more to quantify an amount equivalent to 2.4 μg per batch of the final product.

[0018] At this time, the above step (b) comprises: (b1) a step of pre-treating the above Cynanchum wilfordii extract powder for 2-4 hours in an environment of 25-35℃ temperature and 40-50% humidity; (b2) a step of wet-treating the above Sophora japonica fruit extract powder for 5-15 minutes with purified water adjusted to pH 6.0-7.0 in a weight ratio of 1:0.15-0.25; (b3) a step of preventing oxidation of the above soybean extract powder for 30-60 minutes at a temperature of 15-25℃ in a sealed container in which the oxygen concentration is adjusted to 1% or less by replacing it with nitrogen gas with a purity of 99% or higher; and (b4) a step of preparing a first preliminary mixture by first mixing the above pre-treated Cynanchum wilfordii extract powder and the above wet-treated Sophora japonica fruit extract powder in a weight ratio of 1:2.0-2.5. (b5) a step of stirring the first premixture using a ribbon mixer at 50-80 rpm for 5-10 minutes; (b6) a step of second mixing at 30-50 rpm for 10-15 minutes while slowly adding the antioxidant-treated soybean extract powder to the stirred first premixture; (b7) a step of drying the second mixture at a temperature of 40-60℃ for 30-90 minutes and then homogenizing it by screening it with a 100-150 mesh vibrating screen; (b8) a step of preparing the plant extract mixture by aging the homogenized mixture in a sealed container at a temperature of 20-25℃ for 45-60 minutes;

[0019] At this time, step (c) comprises: (c1) a step of pre-treating the pomegranate concentrate powder for 2.5-3.5 hours under conditions of a temperature of 28-32℃ and a relative humidity of 32-38%; (c2) a step of measuring the enzyme activity of the bromelain powder at a wavelength of 280 nm using a spectrophotometer and standardizing it to 2200-2800 GDU / g; (c3) a step of introducing the pre-treated pomegranate concentrate powder into a V-type mixer and pre-stirring it at 22-28 rpm for 3.5-4.5 minutes; (c4) a step of adding the standardized bromelain powder to the pre-stirred pomegranate concentrate powder in an evenly divided manner over 5-8 minutes at a weight ratio of 11:1-13:1 of the pomegranate concentrate powder to the bromelain powder; (c5) a step of first mixing the above mixture at 45-55 rpm for 16-19 minutes while maintaining a temperature of 20-23℃; (c6) a step of enzyme stabilization treatment by adding 0.02-0.04 parts by weight of ascorbic acid as an antioxidant to the above first mixture per 100 parts by weight of the pomegranate concentrate powder; (c7) a step of second mixing the above enzyme-stabilized mixture at 28-32 rpm for 11-14 minutes; (c8) a step of homogenizing the particle size by sieving the above second mixture through a 90-110 mesh sieve; (c9) a step of preparing the above functional mixture by aging the above homogenized mixture at a temperature of 16-19℃ for 30-42 hours while storing it in a nitrogen-substituted airtight container;

[0020] At this time, the above step (d) comprises: (d1) a step of confirming a purity of 78% or higher by HPLC while storing the vitamin B1 (hydrochloride) for 24-48 hours in an environment with a temperature of 15-25℃ and a relative humidity of 30% or lower; (d2) a step of analyzing and confirming a purity of 100% by UV spectroscopy while storing the vitamin B2 in a UV-blocking container for 12-36 hours; (d3) a step of verifying a purity of 82% or higher by HPLC for 6-24 hours in a sealed container replaced with nitrogen gas; (d4) a step of confirming by UV spectroscopy that the vitamin B12 is diluted to a purity of 1.0% or higher using purified water while storing it at a refrigeration temperature of 2-8℃ for 12-48 hours; (d5) a step of preparing a water-soluble vitamin mixture by first pre-mixing the above-mentioned purity-verified vitamin B1 (hydrochloride), the above-mentioned vitamin B2, and the above-mentioned vitamin B6 hydrochloride in a weight ratio of 1:0.94±0.05:1.23±0.05; (d6) a step of mixing the above-mentioned water-soluble vitamin mixture using a low-speed stirrer at 30-50 rpm for 3-5 minutes until the color of the mixture becomes uniform; (d7) a step of second mixing at 20-30 rpm for 5-8 minutes while slowly adding the above-mentioned diluted vitamin B12 to the above-mentioned water-soluble vitamin mixture in a weight ratio of 1:0.16±0.02 of the water-soluble vitamin mixture to vitamin B12, until no aggregation of particles is observed; (d8) a step of homogenizing the particle size by sieving the above-mentioned second mixture through a 200-300 mesh sieve until the passing rate is 95% or more; (d9) The completion of stabilization is determined by confirming that the moisture content is 3.0% or less and there is no change in the particle size distribution, and the homogenized mixture is sealed in a light-blocking container and stabilized at a temperature of 10-20℃ for 12-24 hours to produce the vitamin complex; the step includes.

[0021] At this time, the above step (e) comprises: (e1) a step of introducing the crystalline cellulose 102 into a ribbon-type or V-type large-capacity mixer (capacity of 50L or more) and pre-mixing it at 30-50 rpm for 2-3 minutes in an environment of 20-25℃ temperature and 40-50% relative humidity; (e2) a step of first mixing at 40-60 rpm for 8-12 minutes while slowly adding the plant extract mixture to the pre-mixed crystalline cellulose 102 in an amount corresponding to 15-25% of the target total weight of the final composition; (e3) a step of second mixing at 50-70 rpm for 15-20 minutes while adding the functional mixture to the first mixture in three equal portions, each corresponding to 60-70% of the target total weight of the final composition, and pre-mixing for 2-3 minutes after each addition. (e4) A step of tertiary mixing at 30-45 rpm for 10-15 minutes while evenly dispersing the vitamin complex in the secondary mixture in an amount corresponding to 1.5-2.5% of the target total weight of the final composition; (e5) A step of final homogenization mixing of the secondary mixture at 60-80 rpm for 25-35 minutes to ensure particle size uniformity until particle size deviation within ±10% and color uniformity are visually confirmed; (e6) A step of removing foreign substances by sieving the final homogenized mixture twice consecutively using a 150-200 mesh vibrating screen; (e7) A step of measuring the moisture content of the sieved mixture by the drying loss method and adjusting it to 3.0% or less by vacuum drying at 40-50℃ if necessary, and confirming homogeneity based on particle distribution and color uniformity visually and under a 100x magnification microscope; (e8) A step of preparing the final composition by filling the mixture with confirmed homogeneity into a sealed container and stabilizing it at a temperature of 15-20℃ for 6-12 hours to achieve physical stabilization and moisture equilibrium between the components;

[0022] At this time, step (f) comprises: (f1) manufacturing tablets of the final composition using a tablet press under conditions of a compression pressure of 8-15 kN and a compression time of 2-5 seconds; (f2) adjusting the hardness of the manufactured tablets to 5-12 kgf by adjusting the compression pressure and verifying the disintegration time within 15-30 minutes; (f3) manufacturing capsules by filling 500-800 mg of the final composition into hard gelatin capsules No. 0 or No. 1 using an automatic capsule filler; (f4) managing the weight deviation of the manufactured capsules within ±5% and visually inspecting the sealing condition; (f5) manufacturing granules by granulating the final composition using a fluid bed granulator under conditions of an inlet temperature of 60-80℃, an exhaust temperature of 40-50℃, and a spray pressure of 1-3 bar; (f6) a step of adjusting the particle size of the manufactured granules to 14-30 mesh through sieving or grinding and managing the moisture content to 2-4%; (f7) a step of packaging the tablet, capsule, or granule in an aluminum-PTP packaging or HDPE container according to the characteristics of the formulation and storage stability; (f8) a step of managing quality including appearance, weight, content uniformity, disintegration test and microbiological test while storing the packaged product at a temperature of 15-25℃ and a relative humidity of 60% or less;

[0023] A device according to one embodiment may be combined with hardware and controlled by a computer program stored on a medium to execute the method of any one of the methods described above. Effects of the invention

[0024] The present invention significantly improves safety by allowing the cynafoside component of the Cynanchum wilfordii extract powder to naturally regulate hormone balance without side effects on estrogen receptors.

[0025] In addition, the present invention improves the elasticity and volume of breast tissue by effectively promoting collagen synthesis through the interaction of ellagic acid in pomegranate concentrate powder and isoflavones in soybean extract powder.

[0026] In addition, the present invention improves overall bioavailability by enhancing the absorption rate of other active ingredients through the proteolytic activity of bromelain.

[0027] In addition, the present invention provides that the rutin component of Sophora japonica fruit extract powder improves vascular health and promotes circulation, thereby facilitating the supply of nutrients to chest tissues.

[0028] In addition, the present invention promotes overall women's health by efficiently facilitating energy metabolism and hormone synthesis through the optimal mixing ratio of vitamin B complex.

[0029] In addition, the present invention can ensure consistent quality and effectiveness by stably maintaining the active ingredients of each raw material through a step-by-step manufacturing process.

[0030] In addition, the present invention can be manufactured in various formulations such as tablets, capsules, and granules, thereby satisfying consumer preferences and convenience of administration.

[0031] In addition, the present invention uses only natural materials, so side effects are minimized even with long-term use, resulting in excellent safety.

[0032] In addition, the present invention is effectively applied to the improvement of gynecomastia in men and exhibits a hormone balance regulating effect regardless of gender.

[0033] In addition, the present invention provides a reliable alternative treatment option by simultaneously ensuring safety and effectiveness compared to existing hormone replacement therapy. Specific details for implementing the invention

[0034] Embodiments are described in detail below. However, various modifications may be made to the embodiments, and thus the scope of the patent application is not limited or restricted by these embodiments. It should be understood that all modifications, equivalents, and substitutions to the embodiments are included within the scope of the rights.

[0035] Specific structural or functional descriptions of the embodiments are disclosed for illustrative purposes only and may be modified and implemented in various forms. Accordingly, the embodiments are not limited to the specific disclosed forms, and the scope of this specification includes modifications, equivalents, or substitutions that fall within the technical concept.

[0036] Terms such as "first" or "second" may be used to describe various components, but these terms should be interpreted solely for the purpose of distinguishing one component from another. For example, the first component may be named the second component, and similarly, the second component may be named the first component.

[0037] When it is stated that a component is "connected" to another component, it should be understood that it may be directly connected to or coupled with that other component, or that there may be other components in between.

[0038] The terms used in the embodiments are for illustrative purposes only and should not be interpreted as intended to be limiting. Singular expressions include plural expressions unless the context clearly indicates otherwise. In this specification, terms such as "comprising" or "having" are intended to indicate the existence of the features, numbers, steps, actions, components, parts, or combinations thereof described in the specification, and should be understood as not precluding the existence or addition of one or more other features, numbers, steps, actions, components, parts, or combinations thereof.

[0039] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as generally understood by those skilled in the art to which the embodiments pertain. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and should not be interpreted in an ideal or overly formal sense unless explicitly defined in this application.

[0040] The advantages and features of the present invention and the methods for achieving them will become clear by referring to the embodiments described in detail below. However, the present invention is not limited to the embodiments disclosed below but may be implemented in various different forms. These embodiments are provided merely to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the invention, and the present invention is defined only by the scope of the claims.

[0041] In the embodiments of the present invention, unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as generally understood by those skilled in the art to which the present invention pertains. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and should not be interpreted in an ideal or overly formal sense unless explicitly defined in the embodiments of the present invention.

[0042] The shapes, sizes, ratios, angles, numbers, etc. disclosed to describe embodiments of the present invention are exemplary and are not limited to the disclosed matters. Furthermore, in describing the present invention, if it is determined that a detailed description of related known technology may unnecessarily obscure the essence of the present invention, such detailed description is omitted. Where terms such as "comprising," "having," or "consisting of" are used in this specification, other parts may be added unless "only" is used. Where a component is expressed in the singular, it includes cases where it includes the plural unless specifically stated otherwise.

[0043] In interpreting the components, they are interpreted to include a margin of error even in the absence of a separate explicit statement.

[0044] The size and thickness of each disclosed component are disclosed for convenience of explanation and the present invention is not necessarily limited to the size and thickness of the disclosed components.

[0045] The features of each of the various embodiments of the present invention may be combined or combined with one another, either partially or wholly, and as will be fully understood by those skilled in the art, various technical interlocking and operation are possible, and each embodiment may be implemented independently of one another or together in an interlocking relationship.

[0046] The present invention relates to a method for preparing an orally ingestible food composition for improving female breast volume, improving gynecomastia, and improving beauty by regulating estrogen / progesterone balance and promoting collagen synthesis, comprising 3-7 parts by weight of Cynanchum wilfordii Hemsley extract powder, 50-65 parts by weight of pomegranate concentrate powder, 8-12 parts by weight of Sophora japonica fruit extract powder, 8-12 parts by weight of soybean extract powder, 3-7 parts by weight of bromelain powder, 3-7 parts by weight of crystalline cellulose 102, 0.2-0.5 parts by weight of vitamin B1 (hydrochloride), 0.2-0.4 parts by weight of vitamin B2, 0.3-0.5 parts by weight of vitamin B6 hydrochloride, and 0.3-0.6 parts by weight of vitamin B12.

[0047] At this time, (a) a step of preparing raw materials comprising 3-7 parts by weight of Cynanchum wilfordii Hemsley extract powder, 50-65 parts by weight of pomegranate concentrate powder, 8-12 parts by weight of Sophora japonica fruit extract powder, 8-12 parts by weight of soybean extract powder, 3-7 parts by weight of bromelain powder, 3-7 parts by weight of crystalline cellulose 102, 0.2-0.5 parts by weight of vitamin B1 (hydrochloride), 0.2-0.4 parts by weight of vitamin B2, 0.3-0.5 parts by weight of vitamin B6 hydrochloride, and 0.3-0.6 parts by weight of vitamin B12; (b) a step of preparing a plant extract mixture by mixing the above Cynanchum wilfordii extract powder, the above Sophora japonica fruit extract powder, and the above soybean extract powder; and (c) a step of preparing a functional mixture by mixing the above pomegranate concentrate powder and the above bromelain powder; (d) a step of preparing a vitamin complex by mixing the above vitamin B1 (hydrochloride), the above vitamin B2, the above vitamin B6 hydrochloride, and the above vitamin B12; (e) a step of preparing a final composition by sequentially mixing the above plant extract mixture, the above functional mixture, the above vitamin complex, and the above crystalline cellulose 102; and (f) a step of molding the above final composition into a form suitable for oral intake.

[0048] At this time, step (a) is a step of standardizing the Cynanchum wilfordii extract powder to a cyanoside content of 0.2-0.4 wt%, standardizing the pomegranate concentrate powder to an ellagic acid content of 4-6 wt%, the Sophora japonica fruit extract powder to a rutin content of 8-12 wt%, and the soybean extract powder to an isoflavone content of 20-30 wt% by HPLC, adjusting the enzyme activity of the bromelain powder to 2000-3000 GDU / g, and confirming and quantifying the purity of vitamins B1, B2, B6, and B12, and step (b) is a step of pre-treating the Cynanchum wilfordii extract powder at a temperature of 25-35℃, wetting the Sophora japonica fruit extract powder with purified water, and treating the soybean extract powder with nitrogen gas for oxidation prevention, then sequentially mixing them, undergoing first and second mixing, and drying at a temperature of 40-60℃. Step (c) involves preparing a plant extract mixture by homogenizing and then aging at a temperature of 20-25℃ for 45-60 minutes; Step (c) involves pre-treating pomegranate concentrate powder at a temperature of 28-32℃ and standardizing the enzyme activity of bromelain powder to 2200-2800 GDU / g, then mixing the pomegranate concentrate powder and bromelain powder in a weight ratio of 11:1-13:1 in a V-type mixer, adding ascorbic acid as an antioxidant for enzyme stabilization treatment, and then aging in a nitrogen-substituted sealed container for 30-42 hours to prepare a functional mixture; and Step (d) involves confirming the purity of vitamins B1, B2, and B6 to be 78%, 100%, and 82% or higher, respectively, diluting vitamin B12 to 1.0% or higher, and then mixing the water-soluble vitamins in a ratio of 1:0.94±0.05:1.23±0.05 The step of preparing a vitamin complex involves first mixing by weight ratio, adding diluted vitamin B12 at a weight ratio of 1:0.16±0.02 for second mixing, sieving through a 200-300 mesh sieve, and stabilizing at 10-20℃; wherein the above step (e) involves pre-stirring crystalline cellulose 102 in a large-capacity mixer, then adding a plant extract mixture at 15-25% of the target weight of the final composition, a functional mixture at 60-70%, and a vitamin complex at 1.5-2%.The step of preparing a final composition involves sequentially adding at 5% and performing first, second, and third mixing respectively, then finally homogenizing, sifting through 150-200 mesh to adjust the moisture content to 3.0% or less, and stabilizing; and the step (f) involves preparing tablets by pressing the final composition at a compression pressure of 8-15 kN, preparing capsules by filling 500-800 mg into hard gelatin capsules, or preparing granules by using a fluid bed granulator at an inlet temperature of 60-80℃, then adjusting the particle size and moisture content of each formulation, packaging them in aluminum-PTP packaging or HDPE containers, and storing them at a temperature of 15-25℃ while maintaining quality control.

[0049] At this time, the above step (a) comprises: (a1) a step of standardizing the above Cynanchum wilfordii extract powder by HPLC to a cynapaposide content of 0.2-0.4 wt% and drying it for 24-48 hours at 40-60℃ and a relative humidity of 30% or less; (a2) a step of standardizing the above pomegranate concentrate powder by HPLC to an ellagic acid content of 4-6 wt% and storing it at a temperature of 15-25℃ and a humidity of 15% or less; (a3) ​​a step of standardizing the above Sophora japonica fruit extract powder by HPLC to a rutin content of 8-12 wt% and grinding it to 80-120 mesh; (a4) a step of standardizing the above soybean extract powder by HPLC to an isoflavone content of 20-30 wt% and grinding it to 80-120 mesh; and (a5) the above A step of adjusting bromelain powder to an enzyme activity of 2000-3000 GDU / g by spectrophotometry and storing it under refrigeration at 2-8℃; (a6) a step of homogenizing the crystalline cellulose 102 using a vibrator to a particle size of 50-100 μm; (a7) a step of selecting vitamin B1 (hydrochloride) to a purity of 78% or higher and quantifying it to an amount equivalent to 1.2 mg per batch of the final product; (a8) a step of selecting vitamin B2 to a purity of 98% or higher and quantifying it to an amount equivalent to 1.4 mg per batch of the final product; (a9) a step of selecting vitamin B6 hydrochloride to a purity of 82% or higher and quantifying it to an amount equivalent to 1.5 mg per batch of the final product; and (a10) a step of diluting and adjusting vitamin B12 into a premix form with a purity of 1% or higher to an amount equivalent to 2.4 μg per batch of the final product It consists of a quantification step.

[0050] At this time, the above step (b) comprises: (b1) a step of pre-treating the above Cynanchum wilfordii extract powder for 2-4 hours in an environment of 25-35℃ temperature and 40-50% humidity; (b2) a step of wet-treating the above Sophora japonica fruit extract powder for 5-15 minutes with purified water adjusted to pH 6.0-7.0 in a weight ratio of 1:0.15-0.25; (b3) a step of preventing oxidation of the above soybean extract powder for 30-60 minutes at a temperature of 15-25℃ in a sealed container in which the oxygen concentration is adjusted to 1% or less by replacing it with nitrogen gas with a purity of 99% or higher; (b4) a step of preparing a first preliminary mixture by first mixing the above pre-treated Cynanchum wilfordii extract powder and the above wet-treated Sophora japonica fruit extract powder in a weight ratio of 1:2.0-2.5; and (b5) the above first preliminary mixture in a ribbon shape The method comprises the steps of: (b6) stirring at 50-80 rpm for 5-10 minutes using a mixer; (b7) mixing at 30-50 rpm for 10-15 minutes while slowly adding the antioxidant-treated soybean extract powder to the stirred first premix; (b8) preparing the plant extract mixture by aging the homogenized mixture in a sealed container at 20-25℃ for 45-60 minutes after drying at 40-60℃ for 30-90 minutes and then sieving it with a 100-150 mesh vibrating screen; and (b8) preparing the plant extract mixture.

[0051] At this time, step (c) comprises: (c1) a step of pre-treating the pomegranate concentrate powder for 2.5-3.5 hours under conditions of a temperature of 28-32℃ and a relative humidity of 32-38%; (c2) a step of measuring the enzyme activity of the bromelain powder at a wavelength of 280 nm using a spectrophotometer and standardizing it to 2200-2800 GDU / g; (c3) a step of introducing the pre-treated pomegranate concentrate powder into a V-type mixer and pre-stirring it at 22-28 rpm for 3.5-4.5 minutes; (c4) a step of adding the standardized bromelain powder to the pre-stirred pomegranate concentrate powder in an evenly divided manner over 5-8 minutes at a weight ratio of 11:1-13:1 of the pomegranate concentrate powder to the bromelain powder; and (c5) maintaining the mixture at a temperature of 20-23℃ and 45-55 The method comprises the steps of: (c6) mixing the mixture for 16-19 minutes at rpm as a first mixture, adding 0.02-0.04 parts by weight of ascorbic acid as an antioxidant to the first mixture per 100 parts by weight of the pomegranate concentrate powder to perform enzyme stabilization treatment, (c7) mixing the enzyme-stabilized mixture for 11-14 minutes at 28-32 rpm as a second mixture, (c8) sieving the second mixture through a 90-110 mesh sieve to homogenize the particle size, and (c9) storing the homogenized mixture in a nitrogen-substituted airtight container and aging it at a temperature of 16-19℃ for 30-42 hours to produce the functional mixture.

[0052] At this time, the above step (d) comprises: (d1) confirming a purity of 78% or higher by HPLC while storing the vitamin B1 (hydrochloride) for 24-48 hours in an environment with a temperature of 15-25℃ and a relative humidity of 30% or lower; (d2) analyzing and confirming a purity of 100% by UV spectroscopy while storing the vitamin B2 in a UV-blocking container for 12-36 hours; (d3) verifying a purity of 82% or higher by HPLC for 6-24 hours in a sealed container replaced with nitrogen gas; (d4) confirming by UV spectroscopy that the vitamin B12 is diluted to a purity of 1.0% or higher using purified water while storing it at a refrigeration temperature of 2-8℃ for 12-48 hours; and (d5) the vitamin B1 (hydrochloride) with confirmed purity, the vitamin B2, and the vitamin B6 hydrochloride A step of preparing a water-soluble vitamin mixture by first pre-mixing at a weight ratio of 1:0.94±0.05:1.23±0.05; (d6) a step of mixing the water-soluble vitamin mixture using a low-speed stirrer at 30-50 rpm for 3-5 minutes until the color of the mixture becomes uniform; (d7) a step of secondarily mixing at 20-30 rpm for 5-8 minutes while slowly adding the diluted adjusted vitamin B12 to the mixed water-soluble vitamin mixture at a weight ratio of 1:0.16±0.02 of the water-soluble vitamin mixture to vitamin B12, until no particle aggregation is observed; (d8) a step of homogenizing the particle size by sieving the second mixture through a 200-300 mesh sieve until the passing rate is 95% or more; and (d9) confirming that stabilization is complete by verifying that the moisture content is 3.0% or less and there is no change in the particle size distribution. The method comprises the step of determining and sealing the homogenized mixture in a light-blocking container and stabilizing it at a temperature of 10-20℃ for 12-24 hours to produce the vitamin complex.

[0053] At this time, the above step (e) comprises: (e1) a step of introducing the crystalline cellulose 102 into a ribbon-type or V-type large-capacity mixer (capacity of 50L or more) and pre-stirring it at 30-50 rpm for 2-3 minutes in an environment of 20-25℃ temperature and 40-50% relative humidity; (e2) a step of first mixing at 40-60 rpm for 8-12 minutes while slowly adding the plant extract mixture to the pre-stirred crystalline cellulose 102 in an amount corresponding to 15-25% of the target total weight of the final composition; (e3) a step of second mixing at 50-70 rpm for 15-20 minutes while adding the functional mixture to the first mixture in three equal portions, each corresponding to 60-70% of the target total weight of the final composition, and pre-mixing for 2-3 minutes after addition; and (e4) the second A step of performing a third mixing at 30-45 rpm for 10-15 minutes while evenly dispersing the vitamin complex in the mixture in an amount corresponding to 1.5-2.5% of the target total weight of the final composition; (e5) a step of ensuring particle size uniformity by performing a final homogenization mixing of the third mixture at 60-80 rpm for 25-35 minutes until particle size deviation within ±10% and color uniformity are visually confirmed; (e6) a step of removing foreign substances by sieving the finally homogenized mixture twice consecutively using a 150-200 mesh vibrating screen; (e7) a step of measuring the moisture content of the sieved mixture by the drying loss method and adjusting it to 3.0% or less by vacuum drying at 40-50℃ if necessary, and confirming homogeneity based on particle distribution and color uniformity visually and by a 100x magnification microscope; and (e8) filling the mixture with confirmed homogeneity into a sealed container and at a temperature The process consists of the step of preparing the final composition by stabilizing at 15-20℃ for 6-12 hours to achieve physical stabilization and moisture equilibrium between the components.

[0054] At this time, the above step (f) comprises: (f1) manufacturing tablets of the above final composition using a tablet press under conditions of a compression pressure of 8-15 kN and a compression time of 2-5 seconds; (f2) adjusting the hardness of the manufactured tablets to 5-12 kgf by adjusting the compression pressure and confirming the disintegration time to be within 15-30 minutes; (f3) manufacturing capsules by filling 500-800 mg of the above final composition into hard gelatin capsules No. 0 or No. 1 using an automatic capsule filler; (f4) managing the weight deviation of the manufactured capsules within ±5% and visually inspecting the sealing condition; (f5) manufacturing granules by granulating the above final composition using a fluid bed granulator under conditions of an inlet temperature of 60-80℃, an exhaust temperature of 40-50℃, and a spray pressure of 1-3 bar; and (f6) sieving the particle size of the manufactured granules Alternatively, the method comprises the steps of adjusting to 14-30 mesh through grinding and managing the moisture content to 2-4%, (f7) packaging the tablet, capsule, or granule in an aluminum-PTP package or HDPE container according to the characteristics of the formulation and storage stability, and (f8) managing the quality, including appearance, weight, content uniformity, disintegration test, and microbiological test, while storing the packaged product at a temperature of 15-25℃ and a relative humidity of 60% or less.

[0055] The technical reasons, critical significance, and specific implementation methods of the above steps (a) and (a1) to (a10) are as follows.

[0056] (a) Overall overview of the step

[0057] The raw material preparation step of the present invention is an essential process for standardizing the active ingredients of each functional raw material and securing optimal physicochemical properties. The weight ratio of 3-7 parts by weight of Cynanchum wilfordii extract powder, 50-65 parts by weight of pomegranate concentrate powder, 8-12 parts by weight of Sophora japonica fruit extract powder, 8-12 parts by weight of soybean extract powder, 3-7 parts by weight of bromelain powder, and 3-7 parts by weight of crystalline cellulose 102 is an optimal blending ratio established to ensure formulation stability while maximizing the estrogen / progesterone balance regulating effect and the collagen synthesis promoting effect.

[0058] The reason pomegranate concentrate powder accounts for the highest proportion at 50-65 parts by weight is that the powerful antioxidant effect of ellagic acid and its collagen synthesis-promoting action play a key role in the core functions of this composition. 3-7 parts by weight of Cynanchum wilfordii extract powder is the critical range for the estrogen receptor-regulating effect of Cyanafoside to be exerted at a safe level; if it is less than this, the effect is negligible, and if it is more than this, it may cause excessive hormonal stimulation.

[0059] (a1) Standardization and drying of Cynanchum wilfordii extract powder

[0060] Technical reasons and critical significance of numerical range

[0061] Standardizing the cyanoside content of Cynanchum wilfordii extract powder to 0.2-0.4% by weight is a key requirement for ensuring safety for estrogen receptors while exerting a hormone balance regulating effect. According to the provided research paper, Cynanchum wilfordii extract showed an effect in improving menopausal symptoms without exhibiting significant binding affinity for estrogen receptors α and β, which is possible when the cyanoside content is controlled within an appropriate range.

[0062] At a cyanoside content of less than 0.2%, the hormone balance regulating effect is significantly reduced, and at a content exceeding 0.4%, the risk of side effects increases due to excessive stimulation of estrogen receptors. The drying condition of 40-60°C is determined considering the thermal stability of cyanoside; exceeding 60°C accelerates the decomposition of the active ingredient, while below 40°C reduces drying efficiency and poses a risk of microbial growth. A relative humidity of 30% or less is an essential condition for preventing oxidation of cyanoside and moisture absorption of the powder.

[0063] Specific implementation method

[0064] After primary grinding the Cynanchum wilfordii raw material to 80-120 mesh using a grinder, the cyanoside content is quantified through HPLC analysis. If the content falls below the target range, it is adjusted through a concentration process; if it exceeds the range, it is diluted using excipients. The standardized Cynanchum wilfordii extract powder is placed in a stainless steel dryer, set to a temperature of 45-55℃, and dried for 24-48 hours while maintaining a relative humidity of 25-30%. During the drying process, the moisture content is measured every 2 hours and continued until it reaches 3% or less.

[0065] Immediately after drying is complete, store in a nitrogen-substituted airtight container in an environment with a temperature of 15-25℃ and a relative humidity of 30% or less. The dried powder is homogenized to a 100 mesh using a vibrating screen to uniformly adjust the particle size.

[0066] (a2) Standardization and storage of pomegranate concentrate powder

[0067] Technical reasons and critical significance of numerical range

[0068] An ellagic acid content of 4-6% by weight in pomegranate concentrate powder is the optimal concentration for maximizing collagen synthesis promotion and antioxidant effects. Ellagic acid is a powerful polyphenol compound that enhances the activity of enzymes involved in collagen synthesis and protects collagen fibers from free radicals. Below 4%, the collagen synthesis-promoting effect is negligible, and above 6%, the intracellular redox balance may be disrupted due to excessive antioxidant activity.

[0069] A storage temperature of 15-25°C is a condition for maintaining the stability of ellagic acid; if the temperature exceeds 25°C, the decomposition of ellagic acid is accelerated, and if it is below 15°C, changes in physical properties due to crystallization may occur. A humidity of 15% or less is an essential condition for preventing oxidation of ellagic acid and preventing caking of the powder.

[0070] Specific implementation method

[0071] The pomegranate raw material is adjusted to a solid content of 70-80% through a concentration process and then powdered using a spray drying method. The ellagic acid content is quantified at 254 nm using an HPLC-DAD detector, and a Sigma-Aldrich product is used as the standard. If content adjustment is required, the concentration is readjusted or standardized ellagic acid is added.

[0072] Standardized pomegranate concentrate powder is wrapped in light-blocking aluminum foil and stored in an airtight container containing a silica gel desiccant. The temperature of the storage room is maintained at 20±3℃, and the relative humidity is managed at 12-15% using a dehumidifier. Quality is controlled by monitoring the ellagic acid content and moisture content once a month during storage.

[0073] (a3) Standardization and grinding of Sophora japonica fruit extract powder

[0074] Technical reasons and critical significance of numerical range

[0075] A rutin content of 8-12% by weight in Sophora japonica fruit extract powder is the optimal concentration for improving vascular health and enhancing nutrient supply to breast tissue through the promotion of circulation. Rutin improves blood circulation in breast tissue through capillary strengthening action and promotes the delivery of nutrients necessary for collagen synthesis. Below 8%, the vascular strengthening effect is negligible, and above 12%, there is a concern regarding side effects due to excessive vasodilation.

[0076] Grinding to 80-120 mesh is the particle size for optimizing the elution rate and bioavailability of rutin. With large particles smaller than 80 mesh, the elution rate decreases, and with fine particles larger than 120 mesh, the elution rate may actually decrease due to aggregation.

[0077] Specific implementation method

[0078] Sophora japonica fruit is extracted using the ethanol extraction method and then concentrated to prepare an extract powder. The rutin content is quantified at 358 nm using an HPLC-UV detector, and a standard curve is constructed using a rutin standard. If the content falls below the target range, it is adjusted through re-extraction or concentration.

[0079] Standardized extract powder is first ground using a pin mill, and then secondarily ground to 80-120 mesh using an air jet mill. To prevent heat generated during the grinding process, a cooling system is operated, and the grinding speed is adjusted to 3000-5000 rpm. After grinding is complete, the particle size distribution is checked using a sieve, and the process is adjusted until the 80-120 mesh passing rate is 95% or higher.

[0080] (a4) Standardization and grinding of soybean extract powder

[0081] Technical reasons and critical significance of numerical range

[0082] The isoflavone content of 20-30% by weight of the soybean extract powder is a range intended to ensure safety while supporting hormone balance regulation as a plant-based estrogen. Isoflavones alleviate hormone deficiency through estrogen-like action and indirectly promote collagen synthesis. Below 20%, the estrogen-compensating effect is negligible, and above 30%, there is a risk of hormone disruption due to excessive intake of plant-based estrogen.

[0083] Grinding to 80-120 mesh is a condition for maximizing the extraction efficiency and absorption rate of isoflavones. It effectively destroys the cell wall structure of soybeans to promote the release of isoflavones and improves absorption in the digestive tract.

[0084] Specific implementation method

[0085] After roasting soybeans, isoflavones are concentrated by extraction with an ethanol-water mixed solvent. Major isoflavone components such as genistein, daidzein, and glycitein are quantified through HPLC analysis, and the total isoflavone content is adjusted to be in the range of 20-30%.

[0086] Standardized soybean extract powder is first ground using a hammer mill, and then finely ground to 80-120 mesh using a ball mill. During the grinding process, nitrogen gas is injected to prevent oxidation of isoflavones, and the temperature is maintained so as not to exceed 30℃. After grinding is complete, the particle size distribution is homogenized using an electrostatic separator.

[0087] (a5) Adjustment of Bromelain Powder Enzyme Activity and Refrigerated Storage

[0088] Technical reasons and critical significance of numerical range

[0089] An enzymatic activity of 2,000–3,000 GDU / g of bromelain powder represents the optimal activity for promoting the absorption of other active ingredients through protein degradation and for the collagen remodeling process. GDU (Gelatin Digesting Unit) is an indicator of gelatin degradation activity; below 2,000 GDU / g, the protein degradation effect is negligible, resulting in limited improvement in the bioavailability of other ingredients. When exceeding 3,000 GDU / g, there is a concern regarding gastrointestinal irritation or damage to existing collagen structures due to excessive protein degradation.

[0090] A refrigerated storage temperature of 2-8°C is the condition required to inhibit microbial growth while maintaining the activity of the bromelain enzyme. Above 8°C, enzyme activity decreases and the risk of microbial contamination increases, and below 2°C, structural denaturation of the enzyme due to freezing may occur.

[0091] Specific implementation method

[0092] Crude bromelain extracted from pineapple stems is purified through ultrafiltration and ion-exchange chromatography. Enzyme activity is measured using spectrophotometry with a gelatin substrate at 37°C, and the change in absorbance is measured at 280 nm. If the activity falls below the target range, it is adjusted through a concentration process, and if it exceeds the range, it is diluted with an excipient such as lactose.

[0093] Divide standardized bromelain powder into smaller portions, vacuum-pack them, and store them in a refrigerator set to 2-8°C. Install a temperature data logger to minimize temperature fluctuations during storage and monitor enzyme activity once a week. Maintain refrigeration until use, and use immediately after opening to prevent loss of enzyme activity.

[0094] (a6) Homogenization of crystalline cellulose 102

[0095] Technical reasons and critical significance of numerical range

[0096] The particle size of crystalline cellulose 102, 50-100 μm, is the range required to ensure optimal compressibility and disintegration during tablet molding. Fine particles smaller than 50 μm may cause delayed disintegration due to excessive compression, while coarse particles larger than 100 μm result in reduced tablet hardness due to insufficient compressibility. Crystalline cellulose 102 provides excellent compressibility and disintegration as an excipient for direct tablet compression, and a content of 3-7 parts by weight is the optimal ratio for balancing tablet strength and disintegration time.

[0097] Specific implementation method

[0098] Crystalline cellulose 102 is screened using a vibratory sieve. First, coarse particles are removed using a 200 mesh sieve, and then fine particles are separated after passing through a 325 mesh sieve. The fraction corresponding to the target particle size range of 50-100 μm is collected and homogenized.

[0099] The homogenization process involves mixing the particles using a V-type blender at 30 rpm for 15 minutes to homogenize the particle distribution. The particle size distribution is measured using a particle size analyzer, and the composition is adjusted so that particles in the 50-100 μm range make up more than 90%. The homogenized crystalline cellulose is stored in an environment with a humidity of 30% or less to prevent moisture absorption.

[0100] (a7-a10) Standardization and Quantification of Vitamin B Complex

[0101] Technical reasons and critical significance of numerical range

[0102] The purity standards and quantification of vitamins B1, B2, B6, and B12 are conditions for optimizing their role as coenzymes in energy metabolism and hormone synthesis processes. A purity of at least 78% and a content of 1.2 mg of vitamin B1 is the minimum effective amount required for carbohydrate metabolism and maintaining nerve function, while a purity of at least 98% and a content of 1.4 mg of vitamin B2 are essential for energy production and antioxidant enzyme activity.

[0103] A purity of 82% or higher and a content of 1.5 mg of vitamin B6 are necessary for amino acid metabolism and hormone synthesis, and a 1% premix form of vitamin B12 is a condition for ensuring stability and accurate quantification. 2.4 μg of vitamin B12 is the recommended amount required for DNA synthesis and maintaining nerve function.

[0104] Specific implementation method

[0105] The purity of each vitamin is confirmed by HPLC analysis; vitamins B1 and B6 are quantified using reverse-phase chromatography with a C18 column, and vitamin B2 is quantified using a fluorescence detector. Vitamin B12 is quantified by microbiological assay.

[0106] Vitamin B12 is diluted to a 1% concentration using purified water in a light-shielding container to prevent photodegradation, and ascorbic acid is added as a stabilizer. The quantitative amount of each vitamin is weighed using an electronic balance with an accuracy of ±0.1 mg, and the total required amount is calculated considering the product quantity per batch. The quantified vitamins are individually packaged and stored under appropriate conditions until use.

[0107] The technical reasons, critical significance, and specific implementation methods of the above steps (b) and (b1) to (b8) are as follows.

[0108] (b) Overall overview of Step

[0109] The step of preparing the plant extract mixture is a key process for achieving an optimal mixture state by considering the different physicochemical properties of Cynanchum wilfordii extract powder, Sophora japonica fruit extract powder, and soybean extract powder. Each plant extract powder has unique active ingredients and particle characteristics, and it is difficult to obtain a homogeneous mixture through simple physical mixing. Therefore, the core technology of the present invention is to improve mixability through a pretreatment process for each raw material and to maximize the interaction between active ingredients through stepwise mixing.

[0110] Since cynafoside in Cynanchum wilfordii extract powder, rutin in Sophora japonica fruit extract powder, and isoflavones in soybean extract powder each have different solubility and stability, precise process control is required to achieve a homogeneous mixture while maintaining the stability of these components. In particular, the main objective of this step is to maximize the synergistic effect with other plant-based estrogens while maintaining the safety of Cynanchum wilfordii extract on estrogen receptors.

[0111] (b1) Pretreatment of Cynanchum wilfordii extract powder

[0112] Technical reasons and critical significance of numerical range

[0113] The pretreatment conditions for Cynanchum wilfordii extract powder, namely a temperature of 25-35°C and a humidity of 40-50%, are designed to optimize the fluidity of the powder while maintaining the stability of cyanoside. Below 25°C, aggregation between powder particles increases, leading to reduced homogeneity during the subsequent mixing process, while above 35°C, thermal decomposition of cyanoside begins, resulting in a loss of active ingredients.

[0114] At humidity levels below 40%, there is a concern regarding powder scattering and heterogeneous mixing due to static electricity generation, while at levels exceeding 50%, caking occurs due to moisture absorption, causing a rapid decrease in mixing efficiency. A pretreatment time of 2 to 4 hours is the minimum required time to achieve moisture and temperature equilibrium within the powder, and exceeding 4 hours poses a risk of oxidation due to prolonged exposure.

[0115] Specific implementation method

[0116] The Baeksuo extract powder is spread thinly in a stainless steel container and placed into a pretreatment room capable of controlling temperature and humidity. The temperature is set to 30±3℃, and the relative humidity is controlled to 45±3%. A circulation fan is installed inside the pretreatment room to ensure smooth air circulation, and the temperature and humidity are monitored in real time using a temperature and humidity sensor.

[0117] During the pretreatment process, the powder is lightly stirred every hour to ensure uniform temperature and humidity distribution. After the pretreatment is complete, the angle of repose is measured to evaluate the fluidity of the powder, and it is determined to be in the optimal state when it is in the range of 35–40 degrees. The pretreated Cynanchum wilfordii extract powder is immediately fed into the next process to minimize quality changes.

[0118] (b2) Wet treatment of Sophora japonica fruit extract powder

[0119] Technical reasons and critical significance of numerical range

[0120] Wetting the Sophora japonica fruit extract powder is an essential process to improve the release of rutin and to improve mixability with other powders. Purified water adjusted to a pH of 6.0-7.0 is a condition that maximizes the stability of rutin; below pH 6.0, acid hydrolysis of rutin is promoted, leading to a decrease in activity, while above pH 7.0, there is a concern about structural changes due to alkaline decomposition.

[0121] A weight ratio of 1:0.15–0.25 is the optimal ratio for achieving surface activation without excessive wetting of the powder. Below 0.15, the wetting effect is negligible, limiting the improvement in rutin releaseability; above 0.25, the risk of powder aggregation and microbial growth due to excessive moisture increases. A treatment time of 5–15 minutes is a condition designed to prevent excessive moisture penetration while achieving complete wetting of the powder surface.

[0122] Specific implementation method

[0123] Adjust the pH of the purified water to 6.5±0.3 using a phosphate buffer solution and maintain the temperature at 20-25℃. After adding the Sophora japonica fruit extract powder to a mixer, spray the measured pH-adjusted purified water evenly using a sprayer. The spraying process is carried out slowly over 3-5 minutes to prevent localized excessive humidity.

[0124] During the wetting process, a paddle mixer is operated at 20-30 rpm to ensure even distribution of moisture. After the process is completed, the moisture content of the powder is checked using an infrared moisture meter, and it is determined to be in an optimal state when it is within the 8-12% range. The wetted powder is fed into the next process within 30 minutes to prevent moisture loss.

[0125] (b3) Antioxidant treatment of soybean extract powder

[0126] Technical reasons and critical significance of numerical range

[0127] Antioxidant treatment of soybean extract powder is a key process to prevent the oxidative decomposition of isoflavone components and to ensure stability during the subsequent mixing process. A nitrogen gas purity of 99% or higher is the minimum condition for effectively replacing oxygen; if the purity is lower than this, the oxidation of isoflavones due to residual oxygen continues.

[0128] An oxygen concentration of 1% or less is a critical condition for inhibiting the auto-oxidation of isoflavones, and when it exceeds 1%, oxidation products of genistein and daidzein are formed, leading to a decrease in estrogen-like activity. A treatment temperature of 15-25°C is a condition considering the thermal stability of isoflavones, and when it exceeds 25°C, temperature-dependent oxidation is accelerated. A treatment time of 30-60 minutes is the time required for complete gas exchange inside the container and removal of oxygen from within the powder.

[0129] Specific implementation method

[0130] Soybean extract powder is placed into a sealed container capable of nitrogen substitution, and nitrogen gas equivalent to three times the container's capacity is injected to perform the first substitution. After standing for 30 minutes, the gas inside the container is released, and the second substitution is performed using the same method. The oxygen concentration is monitored in real time using an oxygen analyzer, and the process is repeated until it stabilizes within the range of 0.5-1.0%.

[0131] During processing, the container is stored in a constant temperature room set to 20±3℃ to minimize temperature fluctuations. After processing is complete, the color change of the powder is visually checked, and it is considered normal when no browning is observed. The antioxidant-treated soybean extract powder is transferred to the next process while maintaining a nitrogen atmosphere.

[0132] (b4) Preparation of the first premixture

[0133] Technical reasons and critical significance of numerical range

[0134] A weight ratio of 1:2.0-2.5 between pre-treated Cynanchum wilfordii extract powder and wet-treated Sophora japonica fruit extract powder is a ratio optimized for the interaction between cynafoside and rutin. At this ratio, the antioxidant action of rutin enhances the stability of cynafoside, while simultaneously maximizing the synergy of vascular improvement and hormone regulation effects.

[0135] When the weight ratio is less than 2.0, the protective effect of rutin is negligible, which reduces the stability of cyanoside, and when it exceeds 2.5, the bioavailability of cyanoside may be impaired due to excessive rutin. The purpose of the first mixing step is to achieve basic dispersion of the two components and to establish a foundation for homogeneous distribution when soybean extract powder is subsequently added.

[0136] Specific implementation method

[0137] First, the pre-treated Cynanchum wilfordii extract powder is placed into a mixer, and the wet-treated Sophora japonica fruit extract powder is weighed and slowly added. The addition is carried out in evenly divided portions over 3-5 minutes to prevent local concentration imbalances.

[0138] The two powders are mixed at a low speed using a simple paddle mixer, without using a ribbon mixer. The mixing speed is set to 15-25 rpm to achieve sufficient dispersion while preventing damage to the powders. The mixing time is 8-12 minutes, and the process is continued until the color becomes uniform to the naked eye. The homogeneity of the first premixture is confirmed by microscopic observation through sampling.

[0139] (b5) Stirring the first premixture

[0140] Technical reasons and critical significance of numerical range

[0141] Stirring at 50-80 rpm using a ribbon mixer is a process to further improve the homogeneity of the first premixture and to create an optimal condition for adding soybean extract powder. A ribbon mixer can achieve fine dispersion between powders through three-dimensional mixing action, but the mixing effect is negligible below 50 rpm, and damage to powder particles is a concern due to excessive shear force above 80 rpm.

[0142] The stirring time of 5 to 10 minutes is the time required to achieve sufficient mixing through the rotation of the ribbon; mixing is incomplete if it is less than 5 minutes, and if it exceeds 10 minutes, electrostatic generation and powder aggregation increase due to overmixing. The homogeneity achieved at this stage is an important factor determining the overall mixing quality when soybean extract powder is subsequently added.

[0143] Specific implementation method

[0144] The first pre-mixture is fed into a ribbon mixer and filled to 60-70% of the mixer's capacity. Before starting to mix, the inside of the mixer is visually inspected to ensure there are no foreign substances, and the rotation status of the ribbon is checked.

[0145] Set the stirring speed to 65±10 rpm and alternate forward and reverse rotation every 2 minutes for uniform mixing. During stirring, close the mixer lid to prevent powder scattering, and visually check the mixing status after a short pause every 3 minutes. After stirring is complete, evaluate the fluidity of the mixture to confirm that it is suitable for the next process.

[0146] (b6) Addition of soybean extract powder and secondary mixing

[0147] Technical reasons and critical significance of numerical range

[0148] The reason for lowering the stirring speed to 30-50 rpm during the second mixing step is to achieve a homogeneous mixture while protecting the isoflavone components of the antioxidant-treated soybean extract powder. Since the soybean extract powder has already had its oxidation suppressed through nitrogen treatment, the influx of air due to excessive stirring must be minimized.

[0149] At speeds below 30 rpm, it is difficult to sufficiently mix the three powders, and at speeds exceeding 50 rpm, there is a concern about the re-oxidation of isoflavones due to the influx of air. A mixing time of 10-15 minutes is the necessary time for the soybean extract powder to be evenly dispersed in the existing mixture, and if it exceeds 15 minutes, the risk of temperature rise and oxidation increases due to prolonged stirring.

[0150] The gradual addition method is intended to prevent rapid changes in the concentration of soybean extract powder and minimize local aggregation.

[0151] Specific implementation method

[0152] Prepare antioxidant-treated soybean extract powder in 3-4 portions and store each portion in a separate container. Adjust the stirring speed of a ribbon mixer to 40±5 rpm and slowly add the first portion. Add the mixture evenly over 1-2 minutes, and mix for 2-3 minutes after the addition is complete.

[0153] Subsequently, the remaining divided amounts are added sequentially using the same method, ensuring sufficient mixing time after each addition. After the final addition is complete, mix for an additional 5 minutes to achieve overall homogeneity. Monitor the temperature rise during the mixing process to ensure it does not exceed 30℃, and regulate the temperature through intermediate breaks if necessary.

[0154] (b7) Drying and homogenization

[0155] Technical reasons and critical significance of numerical range

[0156] The drying temperature of 40-60°C for the secondary mixture is a condition designed to remove moisture increased by the wetting treatment of Sophora japonica fruit extract powder while maintaining the stability of heat-sensitive active ingredients. Below 40°C, drying efficiency decreases, posing a risk of microbial growth due to residual moisture, and above 60°C, thermal decomposition of isoflavones and cyanoside begins.

[0157] The drying time of 30 to 90 minutes is intended to control the moisture content of the mixture to 3% or less; drying is incomplete if the time is less than 30 minutes, and there is a concern about the loss of active ingredients due to over-drying if the time exceeds 90 minutes. Screening through a 100-150 mesh vibrating screen is a process to remove aggregates that may occur during the drying process and to achieve a uniform particle size distribution.

[0158] Specific implementation method

[0159] The secondary mixture is fed into a fluidized bed dryer, and the inlet temperature is set to 50±5℃. The humidity of the drying air is maintained at 10% or less, and the flow rate is adjusted to a level where the mixture can flow properly. During the drying process, the moisture content is measured every 15 minutes to check whether the target moisture content has been achieved.

[0160] After drying is complete, the mixture is cooled to room temperature and then fed into a 100-150 mesh double vibrator. The vibration intensity is set to a medium level, and the mixture is vibrated continuously for 5-10 minutes to remove coarse particles and aggregates. The particle size distribution of the passed powder is analyzed by laser diffraction to confirm homogeneity, and re-sorting is performed if necessary.

[0161] (b8) Aging and completion of plant extract mixture

[0162] Technical reasons and critical significance of numerical range

[0163] The aging process is an essential step for the active ingredients of the three plant extract powders to be physically stabilized and for their mutual chemical interactions to reach equilibrium. A temperature of 20-25°C is a condition where the molecular motion of the active ingredients is properly activated without thermal decomposition, and an aging time of 45-60 minutes is the minimum required time to achieve interaction equilibrium at the molecular level.

[0164] If the exposure time is less than 45 minutes, the interactions between components are incomplete, which may lead to separation in subsequent processes; if it exceeds 60 minutes, the risk of oxidation due to prolonged exposure increases. The use of a sealed container is a condition designed to prevent oxidation by blocking contact with external air and to inhibit moisture absorption. The stability achieved at this stage is a critical factor determining the quality and shelf life of the final product.

[0165] Specific implementation method

[0166] The homogenized mixture is placed into a stainless steel sealed container, and the inside of the container is replaced with nitrogen gas to adjust the oxygen concentration to 2% or less. The container is stored in an aging room set to 22±2℃, and the temperature and humidity are monitored in real time.

[0167] During the aging process, the container must be kept sealed, but the container must be gently rotated every 20 minutes to prevent sedimentation of the mixture. After aging is complete, the color uniformity and fluidity of the mixture are finally checked, and the dispersion status of each component is examined through microscopic observation. The finished plant extract mixture is immediately transferred to the next process or temporarily stored under appropriate storage conditions.

[0168] The technical reasons, critical significance, and specific implementation methods of the above steps (c) and (c1) to (c9) are as follows.

[0169] (c) Overall overview of the stage

[0170] The functional mixture preparation step is a key process designed to maximize synergistic effects by optimizing the ellagic acid in pomegranate concentrate and the proteolytic enzyme activity of bromelain powder. The combination of pomegranate concentrate and bromelain powder performs complex functions, simultaneously promoting collagen synthesis and enhancing the bioavailability of other active ingredients. The ellagic acid in pomegranate concentrate enhances the stability of collagen fibers through powerful antioxidant action, while bromelain promotes nutrient absorption through protein degradation and supports the collagen remodeling process.

[0171] The most critical technical challenge at this stage is to achieve a homogeneous mixture with pomegranate concentrate powder while maintaining the activity of the bromelain enzyme. Since bromelain is an enzyme sensitive to temperature and pH, temperature control during the mixing process and stabilization through the addition of antioxidants are essential.

[0172] (c1) Pretreatment of pomegranate concentrate powder

[0173] Technical reasons and critical significance of numerical range

[0174] The pretreatment conditions for pomegranate concentrate powder, namely a temperature of 28-32°C and a relative humidity of 32-38%, are designed to enhance mixing compatibility with bromelain while maintaining the optimal activity of ellagic acid. Below 28°C, the crystal structure of the pomegranate concentrate powder is rigid, which limits intermolecular interactions with bromelain, while above 32°C, thermal decomposition of ellagic acid begins, leading to a decrease in antioxidant activity.

[0175] A relative humidity range of 32-38% is the optimal condition considering the hygroscopicity of pomegranate concentrate powder. At low humidity below 32%, aggregation due to electrostatic generation in the powder increases, and at humidity exceeding 38%, caking occurs due to excessive moisture absorption, which reduces the homogeneity of the mixture. A pretreatment time of 2.5-3.5 hours is the minimum required time to achieve moisture and temperature equilibrium within the pomegranate concentrate powder.

[0176] Specific implementation method

[0177] Spread the pomegranate concentrate powder evenly on a stainless steel tray to a thickness of 2-3 cm. Set the temperature to 30±2℃ and the relative humidity to 35±3% using a constant temperature and humidity chamber, and then add the pomegranate concentrate powder. Install a temperature and humidity data logger inside the pretreatment room to perform real-time monitoring, and record the temperature and humidity every 30 minutes.

[0178] During the pretreatment process, the powder is lightly mixed with a stainless steel spatula every hour to ensure exposure to uniform conditions. After pretreatment is complete, the moisture content is measured using an infrared moisture meter and verified to be within the range of 2.5-3.0%. The pretreated pomegranate concentrate powder is immediately transferred to the next stage to prevent quality degradation.

[0179] (c2) Standardization of Bromelain Powder Enzyme Activity

[0180] Technical reasons and critical significance of numerical range

[0181] Standardizing the enzymatic activity of bromelain powder to 2200-2800 GDU / g is a condition for maximizing the proteolytic effect and the nutrient absorption-promoting effect at the optimal mixing ratio with pomegranate concentrate powder. Below 2200 GDU / g, the effect of enhancing the bioavailability of other active ingredients is limited, and in particular, the absorption rate of cinafoside from Cynanchum wilfordii extract powder and isoflavones from soybean extract powder is significantly reduced.

[0182] At high activity levels exceeding 2800 GDU / g, excessive proteolysis can damage the pectin structure of pomegranate concentrate powder, potentially reducing the stability of ellagic acid. Additionally, there is an increased risk of gastrointestinal irritation upon consumption of the final product. Measurement at a wavelength of 280 nm is a standard method for accurately measuring enzyme activity by specifically detecting aromatic amino acid residues of bromelain.

[0183] Specific implementation method

[0184] Accurately weigh 1 g of bromelain powder sample and dissolve it in phosphate buffer solution (pH 6.0) to make 100 mL. Filter the dissolved sample through a 0.45 μm filter, and then measure the absorbance at 280 nm using a UV-Vis spectrophotometer. Calculate the enzyme activity based on the calibration curve prepared using standard bromelain.

[0185] If the enzyme activity falls below the target range, it is adjusted through a concentration process; if it exceeds the range, it is diluted using microcrystalline cellulose. The standardization process is carried out under refrigerated conditions of 2-8°C to minimize the loss of enzyme activity. The standardized bromelain powder is vacuum-packed and refrigerated, maintaining a low temperature until immediately before use.

[0186] (c3) V-type mixer pre-stirring

[0187] Technical reasons and critical significance of numerical range

[0188] Preliminary stirring using a V-type mixer is intended to create optimal conditions for the homogeneous dispersion of pomegranate concentrate powder and the addition of bromelain powder. A stirring speed of 22-28 rpm is a range designed to prevent aggregation of the pomegranate concentrate powder while simultaneously minimizing the generation of static electricity. Below 22 rpm, localized aggregation occurs due to insufficient fluidity of the powder, and above 28 rpm, the ellagic acid crystal structure may be damaged due to excessive shear force.

[0189] A preliminary stirring time of 3.5 to 4.5 minutes is the optimal time to achieve complete fluidization of the pomegranate concentrate powder. If the time is less than 3.5 minutes, local concentration variations occur when subsequent bromelain powder is added due to the heterogeneous dispersion state, and if the time exceeds 4.5 minutes, there is a concern about powder damage and electrostatic accumulation due to excessive stirring.

[0190] Specific implementation method

[0191] Wash the container of the V-type mixer with ethanol and dry it completely. Add the pre-treated pomegranate concentrate powder to fill 40-50% of the mixer's capacity, and replace the inside of the mixer with nitrogen gas to adjust the oxygen concentration to 5% or less. Set the mixer to 25±3 rpm and perform preliminary stirring for 4±0.5 minutes.

[0192] During the stirring process, the mixing status is visually checked every minute, and if localized aggregation or wall adhesion is observed, stirring is temporarily stopped and removed using a scraper. After preliminary stirring is completed, the fluidity of the powder is checked by measuring the angle of repose, and the next step is performed when it is in the range of 30-35°.

[0193] (c4) Divided addition of bromelain powder

[0194] Technical reasons and critical significance of numerical range

[0195] A weight ratio of 11:1 to 13:1 of pomegranate concentrate powder to bromelain powder is a formulation ratio designed to achieve the optimal balance between the antioxidant effect of ellagic acid and the proteolytic effect of bromelain. At a ratio less than 11:1, the bromelain content is excessive, which excessively degrades the pectin structure of the pomegranate concentrate powder, thereby impairing the sustained-release characteristics of ellagic acid. At a ratio greater than 13:1, the bromelain content is insufficient, which limits the effect of enhancing the bioavailability of other active ingredients.

[0196] A split addition time of 5-8 minutes is a condition to ensure homogeneous dispersion of bromelain powder while minimizing the loss of enzyme activity. Rapid addition of less than 5 minutes causes enzyme aggregation due to the formation of localized high-concentration zones, and delayed addition of more than 8 minutes results in a decrease in activity due to increased exposure time of bromelain to the atmosphere.

[0197] Specific implementation method

[0198] Divide the standardized bromelain powder into three equal parts and load each into a vibrating feeder. Slowly add the first portion to a V-type mixer while simultaneously starting to stir. Adjust the addition speed to 15-20% of the total amount per minute, and mix for 1-2 minutes after adding each portion to homogenize.

[0199] During the process of adding bromelain powder, the internal temperature of the mixer is monitored using an infrared thermometer to ensure it does not exceed 25℃. If a temperature rise is observed, the addition is temporarily suspended, the cooling fan is activated to lower the temperature, and then the process is resumed. After the entire addition is complete, the weight ratio is checked using an electronic scale to verify that it falls within the target range.

[0200] (c5) 1st mixing

[0201] Technical reasons and critical significance of numerical range

[0202] The primary mixing conditions of a temperature of 20-23℃ and a stirring speed of 45-55 rpm are designed to promote intermolecular interactions with pomegranate concentrate powder while maintaining the optimal activity of bromelain enzymes. Below 20℃, the enzyme activity of bromelain decreases significantly, limiting the proteolytic effect, while above 23℃, the risk of enzyme denaturation increases.

[0203] A stirring speed of 45–55 rpm is the range required to provide sufficient mixing force while preventing damage to the enzyme structure due to shear stress. Below 45 rpm, local concentration variations occur due to non-uniform mixing, and above 55 rpm, there is a concern regarding a decrease in bromelain activity due to excessive mechanical stress. A mixing time of 16–19 minutes is the optimal time to achieve complete homogenization.

[0204] Specific implementation method

[0205] A cooling system is installed around the V-type mixer, and the internal temperature of the mixer is maintained at 21.5±1.5℃. The stirring speed is set to 50±5 rpm, and primary mixing is performed for 17.5±1.5 minutes. During the mixing process, sampling is performed every 3 minutes to check the homogeneity of the mixture under a microscope.

[0206] For the evaluation of mixing homogeneity, samples are collected from five randomly selected points to observe the distribution of bromelain. Homogeneous mixing is determined to be complete when the deviation in bromelain concentration between points is within 5%. Immediately after the mixing is complete, proceed to the next step to minimize the loss of bromelain activity.

[0207] (c6) Enzyme stabilization through the addition of ascorbic acid

[0208] Technical reasons and critical significance of numerical range

[0209] 0.02 to 0.04 parts by weight of ascorbic acid added is the optimal concentration that prevents oxidative damage to the bromelain enzyme while not inhibiting the interaction with ellagic acid in pomegranate concentrate powder. Ascorbic acid is a powerful reducing agent that protects the cysteine ​​residues of bromelain from oxidation, thereby stabilizing enzyme activity. Below 0.02 parts by weight, the antioxidant effect is insufficient, which accelerates the decline in bromelain activity, and above 0.04 parts by weight, the stability of ellagic acid may be reduced due to an excessive reducing environment.

[0210] The addition of ascorbic acid also provides an additional effect of improving the preservation stability of the final product. Setting the relative amount added relative to 100 parts by weight of pomegranate concentrate powder is a method to ensure a constant stabilization effect regardless of batch size.

[0211] Specific implementation method

[0212] Ascorbic acid is prepared in the form of a fine powder and passed through an ionization device to prevent static electricity. Ascorbic acid is accurately weighed and added to the mixture after the first mixing is completed, at a ratio of 0.03 ± 0.01 parts by weight based on the weight of the pomegranate concentrate powder. The addition is evenly dispersed over 30 seconds using a vibrating feeder.

[0213] During the ascorbic acid addition process, rotate a V-type mixer at a low speed of 15-20 rpm to ensure immediate dispersion. After the addition is complete, measure the pH of the mixture using a pH meter and check if it is within the range of 5.5-6.5. If the pH falls outside this range, add a small amount of buffer to adjust it.

[0214] (c7) Secondary mixing

[0215] Technical reasons and critical significance of numerical range

[0216] A stirring speed of 28-32 rpm for the second mixing is the optimal condition for re-homogenization of the mixture with added ascorbic acid. The reason for applying a lower speed than the first mixing is to achieve only the uniform dispersion of ascorbic acid while maintaining the interaction structure of the already formed bromelain and pomegranate concentrate powder. Below 28 rpm, the dispersion of ascorbic acid is incomplete, resulting in local concentration variations, and above 32 rpm, the previously formed intermolecular interactions may be damaged.

[0217] A mixing time of 11-14 minutes is the time required for the complete dispersion of ascorbic acid and the completion of the stabilization reaction. During this process, ascorbic acid forms a protective barrier around the active site of bromelain to prevent oxidative damage.

[0218] Specific implementation method

[0219] The stirring speed of the V-type mixer is reset to 30±2 rpm, and a second mixing is performed for 12.5±1.5 minutes. During the mixing process, the inside of the mixer is continuously replaced with nitrogen gas to maintain the oxygen concentration at 3% or less. Sampling is performed every 2 minutes to check the dispersion state of ascorbic acid by iodine titration.

[0220] Mixing homogeneity is evaluated by measuring ascorbic acid concentrations in samples taken from eight randomly selected points. Homogeneous mixing is determined to be complete when the concentration deviation between points is within 3%. After the second mixing is completed, bromelain activity is re-measured to confirm the stabilization effect.

[0221] (c8) Particle size homogenization

[0222] Technical reasons and critical significance of numerical range

[0223] Screening using a 90-110 mesh sieve is an important process for optimizing the final formulation characteristics and bioavailability of functional mixtures. Coarse particles smaller than 90 mesh (approx. 165 μm) cause non-uniform density distribution during tablet compression, which adversely affects disintegration properties, while fine particles larger than 110 mesh (approx. 140 μm) can accelerate the loss of activity of bromelain due to an excessive increase in surface area.

[0224] Particle size homogenization is also essential for standardizing the release characteristics of the final product. Uniform particle size ensures a constant dissolution rate in the digestive tract, making the absorption pattern of the active ingredient predictable.

[0225] Specific implementation method

[0226] Install 90 mesh and 110 mesh sieves in sequence on the vibrating sieve and set the vibration intensity to an intermediate level. Sift the mixture, after the second mixing is complete, while slowly feeding it in over 30 minutes. Coarse particles that do not pass through the 90 mesh are separated, re-ground, and then sieved again.

[0227] Fine particles that pass through the 110 mesh are collected separately and their particle size is adjusted through aggregation treatment. The fraction corresponding to the target particle size range is collected in an anti-static container, and an ionization device is operated to eliminate static electricity that may occur during the sieving process. Finally, the particle size distribution is measured using laser diffraction, and it is confirmed that particles in the 90-110 mesh range account for at least 85%.

[0228] (c9) Aging in a nitrogen-substituted environment

[0229] Technical reasons and critical significance of numerical range

[0230] Aging in a nitrogen-substituted environment is an essential process for stabilizing the activity of bromelain enzymes and optimizing interactions with pomegranate concentrate powder. An aging temperature of 16–19°C is a temperature range in which intermolecular interactions can proceed sufficiently while maintaining the enzymatic activity of bromelain. Below 16°C, molecular motion is restricted, delaying the formation of interactions, and above 19°C, the risk of bromelain autolysis increases.

[0231] An aging time of 30 to 42 hours is the optimal time for forming the optimal interaction structure between bromelain and pomegranate concentrate powder. If the aging time is less than 30 hours, the interaction is incomplete, leading to reduced efficacy of the final product, while if it exceeds 42 hours, there is a concern about a decrease in bromelain activity due to excessive aging. Nitrogen substitution is a condition designed to prevent oxidative damage and inhibit microbial growth.

[0232] Specific implementation method

[0233] Clean a stainless steel airtight container with ethanol and dry it completely. Replace the inside of the container three times with nitrogen gas of 99.9% or higher purity to adjust the oxygen concentration to 1% or less. Pour the mixture, with the particle size homogenized, into the container to fill it to 60-70% of its capacity and seal it immediately.

[0234] The temperature of the aging room is set to 17.5±1.5℃ and continuously monitored using a temperature and humidity data logger. During the aging process, the container is gently rotated every 12 hours to prevent separation of components due to gravity. After 36±6 hours of aging, the bromelain activity is re-measured, and it is confirmed that at least 90% of the initial activity is maintained. Once aging is complete, the functional mixture is immediately transferred to the next process or refrigerated to maintain quality.

[0235] The technical reasons, critical significance, and specific implementation methods of the above steps (d) and (d1) to (d9) are as follows.

[0236] (d) Overall overview of Step

[0237] The vitamin complex manufacturing step is a key process for achieving optimal bioavailability while ensuring the stability of water-soluble vitamins. Vitamins B1, B2, B6, and B12 act as essential coenzymes for energy metabolism, hormone synthesis, and neurotransmitter production, and play a crucial role in maximizing the estrogen / progesterone balance regulating effect of the present invention. Since the physicochemical properties of each vitamin differ, individual pretreatment processes and stepwise mixing methods are essential.

[0238] (d1) Verification of Vitamin B1 (Hydrochloride) Purity and Storage

[0239] Technical reasons and critical significance of numerical range

[0240] The standard of a purity of 78% or higher for vitamin B1 hydrochloride is the optimal purity that ensures physiological activity as thiamine while considering manufacturing economics. Below 78%, the coenzyme function of thiamine is significantly reduced, resulting in minimal effects in supporting carbohydrate metabolism and nerve function. A temperature of 15-25°C is a condition that takes into account the thermal stability of thiamine; above 25°C, the decomposition of thiamine is accelerated, and below 15°C, a decrease in solubility may occur due to changes in the crystal structure.

[0241] A relative humidity of 30% or less is an essential condition to prevent caking and decomposition reactions caused by the hygroscopicity of thiamine hydrochloride. A storage period of 24 to 48 hours is the minimum time required to confirm the stability of thiamine under temperature and humidity conditions and to monitor changes in quality.

[0242] Specific implementation method

[0243] After weighing vitamin B1 hydrochloride to 110% of the required amount using a precision balance, store it in a temperature and humidity controlled room. Set the temperature of the room to 20±3℃ and maintain the relative humidity at 25-30% using a dehumidifier. Use airtight containers made of stainless steel or glass, and place a silica gel desiccant alongside them.

[0244] HPLC analysis is performed using a C18 reversed-phase column, and gradient elution of 0.1% aqueous trifluoroacetic acid solution and methanol is applied as the mobile phase. The detection wavelength is set to 254 nm, and USP-grade thiamine hydrochloride is used as the standard. Samples are collected at 24-hour intervals to measure purity, and after 48 hours, the final purity is confirmed to be 78% or higher. The purity measurement result is calculated as the average value of three repeated analyses.

[0245] (d2) Vitamin B2 purity verification and light-protected storage

[0246] Technical reasons and critical significance of numerical range

[0247] The 100% purity standard for Vitamin B2 is a strict quality standard that takes into account the photodegradation characteristics of riboflavin. Since Vitamin B2 is highly photosensitized, even trace amounts of impurities can accelerate the photodegradation reaction, making the maintenance of high purity essential. The use of UV-blocking containers is a key condition for preventing the photodegradation of riboflavin and ensuring its stability.

[0248] A storage period of 12 to 36 hours is the time required to verify the stability of riboflavin under light-shielded conditions and to evaluate the degree of photodegradation. If the storage period exceeds 36 hours, fine photodegradation products may accumulate, and if it exceeds 12 hours, the stability evaluation is insufficient.

[0249] Specific implementation method

[0250] After weighing Vitamin B2, store it in a brown glass jar or a container completely shielded from light by aluminum foil. Use LED lighting instead of fluorescent lights in the storage room and block external light by attaching UV-blocking film to the windows. Maintain the temperature at 20±2℃ and the relative humidity at 40-50%.

[0251] UV spectroscopy analysis measures the absorbance of riboflavin at 266 nm and 375 nm. Standard solutions are prepared by dissolving riboflavin in 0.01 N hydrochloric acid, and calibration curves are constructed within a concentration range of 1–10 μg / mL. Samples are collected at 12-hour intervals and performed rapidly under red light to minimize light exposure time during sampling. Purity measurements are conducted in a dark room, and the presence of degradation products, such as lumiflavin and lumichrome, is also checked.

[0252] (d3) Verification of Vitamin B6 Hydrochloride Purity and Nitrogen-Substituted Storage

[0253] Technical reasons and critical significance of numerical range

[0254] The standard of a purity of 82% or higher for vitamin B6 hydrochloride is a condition to ensure manufacturing stability while guaranteeing its coenzyme function as pyridoxine. Below 82%, the formation of pyridoxal phosphate, which is necessary for amino acid metabolism and neurotransmitter synthesis, is reduced. Nitrogen gas substitution is an essential condition to prevent the oxidation reaction of pyridoxine and to ensure long-term stability.

[0255] A storage period of 6 to 24 hours is the optimal time to confirm the stability of pyridoxine in a nitrogen atmosphere and evaluate the degree of oxidation. If the storage period exceeds 24 hours, a minor oxidation reaction may occur, and if it is less than 6 hours, verification of the nitrogen substitution effect is insufficient.

[0256] Specific implementation method

[0257] After weighing vitamin B6 hydrochloride, place it into a vacuum desiccator and completely remove the internal air using a vacuum pump. Inject nitrogen gas with a purity of 99.9% or higher to fill it to atmospheric pressure, and repeat this process three times to adjust the oxygen concentration to 1% or less. Install an oxygen concentration meter inside the desiccator to continuously monitor it.

[0258] HPLC analysis is performed using a C18 column, applying a gradient elution of phosphate buffer (pH 3.0) and methanol as the mobile phase. The detection wavelength is set to 290 nm, and pyridoxamine is used as the internal standard. Samples are collected at 6-hour intervals under a nitrogen atmosphere, and the amounts of oxidation products, pyridoxal and 4-pyridoxic acid, are also measured. The purity analysis results are determined to be stable when the reduction rate from the initial value is within 2%.

[0259] (d4) Vitamin B12 Dilution Adjustment and Refrigeration

[0260] Technical reasons and critical significance of numerical range

[0261] Dilution adjustment of vitamin B12 to 1.0% or higher is an essential condition for the use of minute amounts of cobalamin and accurate quantification. Since vitamin B12 is used in minute amounts in μg units, direct measurement is difficult, so quantification through dilution is necessary. Below 1.0%, dilution error increases, and quantification accuracy decreases.

[0262] A refrigeration temperature of 2–8°C is the optimal condition for maintaining the structural stability of cobalamin. Above 8°C, destabilization of the cobalamin-cobalt bond occurs, and below 2°C, changes in concentration may occur due to the freezing of the aqueous solution. A storage period of 12–48 hours is the time required to verify the stability of the diluted solution and achieve concentration uniformity.

[0263] Specific implementation method

[0264] Weigh the vitamin B12 raw material using a precision balance and add a small amount of purified water to a light-shielded beaker to completely dissolve it. During the dissolution process, perform ultrasonic treatment for 5 minutes to confirm complete dissolution, then add purified water to dilute it to a concentration of 1.0-1.2%. Dispense the diluted solution into a brown reagent bottle and store it in a refrigerator at 2-8°C.

[0265] UV spectroscopy analysis measures the characteristic absorption peak of cobalamin at 361 nm. Standard solutions are prepared by dissolving cyanocobalamin standards in purified water, and calibration curves are constructed within a concentration range of 0.1–2.0 μg / mL. Samples are collected at 12-hour intervals to measure concentration, and after 48 hours, it is confirmed that the change in concentration is within ±3% of the initial value. To prevent temperature fluctuations during storage, a temperature data logger is installed for continuous monitoring.

[0266] (d5) 1st preliminary mixture of water-soluble vitamin mixture

[0267] Technical reasons and critical significance of numerical range

[0268] The weight ratio of Vitamins B1, B2, and B6, 1:0.94±0.05:1.23±0.05, is the optimal blending ratio considering the recommended daily intake and interactions of each vitamin. This ratio reflects the interdependence of each vitamin when acting as a coenzyme in the process of energy metabolism. The tolerance of ±0.05 is a realistic range considering the weighing accuracy and mixing uniformity in the actual manufacturing process.

[0269] A ratio of 0.94 for vitamin B2 is the optimal amount of riboflavin required for the activation of other B vitamins, and a ratio of 1.23 for vitamin B6 reflects the high requirements for amino acid metabolism and neurotransmitter synthesis. If the tolerance is exceeded, the balance of interactions between vitamins may be disrupted, potentially reducing the overall effect.

[0270] Specific implementation method

[0271] Weigh each vitamin with an accuracy of ±0.01 mg using a precision balance. Weigh Vitamins B2 and B6 based on the calculated weight ratio relative to Vitamin B1, and proceed with the weighing order in the order of B2, B6, and B1, in order of lowest hygroscopicity.

[0272] Vitamin B2 is first added to a V-type mixer and pre-rotated for 30 seconds, after which Vitamin B6 is added. After mixing for 2 minutes, Vitamin B1 is gradually added while mixing at 15 rpm for 5 minutes. To prevent static electricity generation during the mixing process, the relative humidity is maintained at 50-60%, and the inner wall of the mixer is treated with an anti-static agent.

[0273] After mixing is complete, samples are taken from 5 locations to analyze the content of each vitamin, and it is confirmed that the relative standard deviation (RSD) is within 5%. If mixing uniformity is not ensured, mixing is performed for an additional 2-3 minutes.

[0274] (d6) Water-soluble vitamin mixture color homogenization mixing

[0275] Technical reasons and critical significance of numerical range

[0276] Color uniformity is an important indicator of the physical uniformity of a vitamin mixture. Mixing at the molecular level is achieved when the yellow of vitamin B2 and the white of other vitamins are completely mixed to produce a uniform light yellow color. Low-speed stirring of 30-50 rpm is the optimal condition for providing sufficient mixing power without physical damage to the vitamin particles.

[0277] If the speed exceeds 50 rpm, there is a risk of vitamin decomposition due to frictional heat, and if it is less than 30 rpm, it is difficult to achieve uniformity due to insufficient mixing power. A mixing time of 3 to 5 minutes is the minimum time required to achieve color uniformity, and if it exceeds 5 minutes, particle refinement may occur due to excessive mixing.

[0278] Specific implementation method

[0279] Add the water-soluble vitamin mixture to the ribbon mixer and set the rotation speed to 40 rpm. Before starting the mixing, replace the inside of the mixer with nitrogen gas to prevent oxidation. During the mixing process, stop the mixer at 1-minute intervals and visually check the color distribution.

[0280] Color uniformity is determined by measuring L*, a*, and b* values ​​at 10 points on the surface of the mixture using a colorimeter, and is judged to be uniform when the relative standard deviation of each value is within 3%. Mixing is continued until a uniform light yellow color is observed overall without any yellow spots or white lumps being observed during visual inspection.

[0281] To prevent temperature rise during mixing, maintain the internal temperature of the mixer at 25°C or lower, and operate the cooling device if necessary. Stop mixing immediately after color uniformity is achieved to prevent excessive mixing.

[0282] (d7) Addition of Vitamin B12 and secondary mixing

[0283] Technical reasons and critical significance of numerical range

[0284] A weight ratio of 1:0.16±0.02 of vitamin B12 to a water-soluble vitamin mixture is the optimal ratio for the trace characteristics of cobalamin and uniform dispersion. The base ratio of 0.16 reflects the daily recommended intake of vitamin B12 (2.4 μg) and the difference in mg-unit content of other vitamins. The tolerance of ±0.02 is a realistic range that takes into account the quantitative error of the diluted vitamin B12 solution and losses during the addition process.

[0285] Low-speed mixing of 20-30 rpm is the condition for uniform dispersion of vitamin B12 and stable mixing with other vitamins. If the speed exceeds 30 rpm, the liquid B12 solution may scatter into droplets and be lost, and if it is less than 20 rpm, uniform dispersion is difficult due to insufficient mixing power. A mixing time of 5-8 minutes is the optimal time to achieve complete mixing without particle aggregation.

[0286] Specific implementation method

[0287] Connect the diluted vitamin B12 solution to the metering pump and slowly add it while the water-soluble vitamin mixture is being mixed. Adjust the addition rate to evenly divide and add the entire B12 solution over 2 to 3 minutes. During the addition process, maintain the mixer's rotation speed at 25 rpm to provide appropriate mixing power.

[0288] After the addition of vitamin B12 is complete, increase the rotation speed of the mixer to 30 rpm and mix for an additional 5 minutes. During the mixing process, observe the state of particle aggregation using a microscope, and continue mixing until no aggregates larger than 5 μm are observed at 100x magnification.

[0289] To prevent an increase in moisture content due to the addition of water, a dehumidifier is operated during mixing to maintain the relative humidity at 40% or lower. After mixing is complete, samples are collected from five locations to check the uniformity of vitamin B12 content and to verify that the relative standard deviation is within 10%.

[0290] (d8) Secondary mixture sieving and particle size homogenization

[0291] Technical reasons and critical significance of numerical range

[0292] Sieving to a 200-300 mesh is a key process for homogenizing the particle size of vitamin complexes and dispersing aggregated particles. Coarse particles larger than 200 mesh (74 μm) cause non-uniform density distribution during tablet compression, while fine particles smaller than 300 mesh (50 μm) optimize dissolution rate and bioavailability. A pass rate of 95% or higher is a standard to ensure the physical uniformity and quality consistency of the product.

[0293] At a pass rate of less than 95%, non-uniform mixing and reduced compressibility may occur due to coarse particles. The sieving process not only separates particles by size but also eliminates particle aggregation caused by electrostatic forces and increases surface area, thereby improving solubility.

[0294] Specific implementation method

[0295] Install 200 mesh and 300 mesh sieves vertically on a vibrating sieve and set the vibration intensity to a medium level. Disperse the secondary mixture evenly over the 200 mesh sieve and vibrate for 10 minutes to perform primary sieving. Coarse particles that did not pass through the 200 mesh are re-ground using a grinder and then sieved again.

[0296] The powder that has passed through a 200 mesh is sieved a second time through a 300 mesh sieve to adjust the final particle size. An ionizer is installed to remove static electricity generated during the sieving process, and the relative humidity of the working environment is maintained at 50-60%.

[0297] The pass rate is calculated by measuring the weight before and after sieving, and if the target pass rate is not met, the vibration time is extended or the vibration intensity is adjusted. After sieving is complete, the particle size distribution is measured using a particle size analyzer, and it is confirmed that the D50 value is in the range of 60-70 μm. The sieved powder is immediately collected in a sealed container to prevent re-absorption.

[0298] (d9) Stabilization of vitamin complex and final manufacturing

[0299] Technical reasons and critical significance of numerical range

[0300] A moisture content of 3.0% or less is a key criterion for ensuring the chemical and microbiological safety of the vitamin complex. If it exceeds 3.0%, the hydrolysis reactions of the vitamins are accelerated, and the risk of microbial growth increases. The absence of change in particle size distribution is an indicator of physical stability, meaning that no particle aggregation or separation occurs during storage.

[0301] A stabilization temperature of 10–20°C is the optimal condition for simultaneously ensuring the stability of all vitamin components. Above 20°C, there is a concern about the decomposition of heat-sensitive vitamins, while below 10°C, there is a risk of increased moisture content due to humidity condensation. A stabilization time of 12–24 hours is the minimum time required to achieve physicochemical equilibrium between the components.

[0302] Specific implementation method

[0303] Fill a brown glass bottle or an aluminum foil laminated container with the sieved vitamin complex. Replace the inside of the container with nitrogen gas to adjust the oxygen concentration to 1% or less, then seal it. To prevent the powder from being compressed during the filling process, gently vibrate the container to allow it to settle naturally.

[0304] Moisture content is measured using an infrared moisture meter or the Karl Fischer titration method. Before measurement, the sample is pre-dried at 105°C for 30 minutes and then cooled in a desiccator. If the moisture content exceeds 3.0%, vacuum drying is performed at 40°C or below to adjust the moisture content to the target level.

[0305] Particle size distribution is measured by comparing D10, D50, and D90 values ​​before and after stabilization using laser diffraction. It is determined to be stable when the rate of change is within ±5%. The temperature of the stabilization room is set to 15±3℃, and the relative humidity is maintained at 30-40%. During the stabilization period, temperature and humidity are recorded at 6-hour intervals, and the final quality is checked after 24 hours to complete the manufacture of the vitamin complex.

[0306] To prevent sudden changes in temperature and humidity, access to the stabilization room is minimized, and entry is permitted via the airlock system only when necessary. Upon completion of stabilization, the material is immediately transferred to the next process to minimize quality degradation.

[0307] The technical reasons, critical significance, and specific implementation methods of the above steps (e) and (e1) to (e8) are as follows.

[0308] (e) Overall overview of the final composition manufacturing steps

[0309] The final composition manufacturing stage is a key process for producing a stable solid composition by homogeneously dispersing plant extract mixtures, functional mixtures, and vitamin complexes with different physicochemical properties. The reason for adopting a sequential mixing method is that the particle size, density, and flowability of each component differ, causing segregation and reduced content uniformity when added simultaneously. In particular, trace components such as vitamin complexes must be dispersed stepwise through a dilution mixing method to ensure content uniformity in the final product.

[0310] The reason for using crystalline cellulose 102 as the base matrix is ​​that it provides excellent compressibility and disintegration while minimizing interactions with other ingredients, thereby ensuring the stability of the active ingredient. The use of a large-capacity mixer is an essential condition for ensuring batch-to-batch uniformity and maximizing manufacturing efficiency at a commercial production scale.

[0311] (e1) Crystalline Cellulose 102 Pre-stirring Step

[0312] Technical reasons and critical significance of numerical range

[0313] A capacity of 50L or more for large-capacity ribbon or V-type mixers is the minimum required to simultaneously ensure economic efficiency and quality uniformity in commercial production. Small capacities under 50L lead to increased batch-to-batch variability and reduced production efficiency, while excessively large capacities may actually result in reduced mixing uniformity. Ribbon mixers minimize damage to powder components due to low shear force, while V-type mixers provide uniform dispersion through convective mixing.

[0314] A temperature of 20-25°C is a condition for suppressing static electricity generation and optimizing the flowability of the powder. Below 20°C, the cohesiveness of the powder increases, leading to a decrease in mixing efficiency, while above 25°C, there is a concern regarding powder adhesion and uneven mixing due to static electricity generation. A relative humidity of 40-50% is the optimal range to suppress static electricity generation in the powder while preventing caking caused by moisture absorption.

[0315] A stirring speed of 30-50 rpm and a time of 2-3 minutes are conditions for the release of aggregation and uniform dispersion of crystalline cellulose. Below 30 rpm, the release of aggregation is insufficient, and above 50 rpm, particle destruction may occur due to excessive shear force. Below 2 minutes, homogenization is insufficient, and above 3 minutes, there is a risk of energy waste and particle damage.

[0316] Specific implementation method

[0317] Before adding crystalline cellulose 102 to a ribbon mixer with a capacity of 50-100L, clean the inside of the mixer with compressed air and perform anti-static treatment. Set the temperature of the mixing chamber to 22±2℃ and adjust the relative humidity to 45±3% using a humidifier and a dehumidifier. Install a temperature and humidity sensor to perform real-time monitoring.

[0318] When adding crystalline cellulose 102 to the mixer, add it slowly to minimize dust generation, and seal the mixer lid after adding is complete. Set the stirring speed to 40±5 rpm and perform preliminary stirring for 2.5 minutes. Monitor torque changes during stirring to check for any abnormalities, and after stirring is complete, visually check for the presence of aggregates through sampling.

[0319] (e2) First mixing step of plant extract mixture

[0320] Technical reasons and critical significance of numerical range

[0321] The reason the plant extract mixture was set to 15-25% of the target total weight of the final composition is that it is the optimal ratio for the concentration of active ingredients and the expression of functionality of the extracts of Cynanchum wilfordii, Sophora japonica fruit, and soybeans. Below 15%, the concentration of the plant active ingredients is insufficient, resulting in a negligible effect on regulating the estrogen / progesterone balance, and above 25%, there is a concern that the sensory quality may deteriorate due to the bitter taste and off-flavor of the plant extracts.

[0322] The gradual addition method is intended to prevent segregation among components with different densities and particle sizes and to ensure uniform dispersion. A stirring speed of 40-60 rpm is a condition for effectively dispersing aggregates of the plant extract mixture while preventing shear damage. A mixing time of 8-12 minutes is the minimum time required to achieve complete dispersion and homogenization.

[0323] Specific implementation method

[0324] Before adding the plant extract mixture, temporarily stop stirring the mixer and open the inlet. Feed the pre-measured plant extract mixture evenly over 5 minutes using a screw feeder. Feed at a rate of 20% of the total amount per minute to prevent segregation.

[0325] Stirring is initiated simultaneously with the addition of the plant extract mixture, and primary dispersion is performed by stirring at 50 rpm for the first 2 minutes. Subsequently, the stirring speed is increased to 55 rpm and mixing is continued for 8 minutes. During the mixing process, sampling is performed every 3 minutes to check for color uniformity and the presence of aggregates. The completion of the primary mixing is determined by confirming that the torque value has stabilized after mixing is complete.

[0326] (e3) Secondary mixing step of functional mixture

[0327] Technical reasons and critical significance of numerical range

[0328] The reason the functional mixture accounts for the highest proportion of 60-70% of the final composition is that pomegranate concentrate powder and bromelain are responsible for the core functionality of this composition. Below 60%, the concentrations of ellagic acid and bromelain are insufficient, so the effect of promoting collagen synthesis is limited, and above 70%, the expression of functionality of other components may be inhibited.

[0329] The method of adding the ingredients in three equal, 1 / 3 portions is intended to prevent uneven mixing caused by the rapid addition of large amounts of ingredients and to achieve optimal dispersion through a stepwise dilution effect. Pre-mixing for 2-3 minutes after each addition is an essential step to ensure homogeneity at each stage. A final mixing time of 15-20 minutes and a stirring speed of 50-70 rpm are conditions for complete homogenization.

[0330] Specific implementation method

[0331] Divide the functional mixture into three equal parts and prepare each in a separate container. Slowly feed the first portion using a screw feeder over a period of 2 minutes while mixing at a stirring speed of 55 rpm. After feeding is complete, perform preliminary mixing for 3 minutes to complete the first dispersion.

[0332] Add the second divided amount in the same manner and perform preliminary mixing for 3 minutes. During this time, check the dispersion state by observing the color change and fluidity of the mixture. Repeat the same preliminary mixing process after adding the third divided amount.

[0333] After all functional mixtures have been added, adjust the stirring speed to 60 rpm and perform final mixing for 18 minutes. During the mixing process, stop the mixer every 5 minutes to scrape off wall adhesions and improve mixing efficiency. After mixing is complete, check the uniformity of the content through multi-point sampling.

[0334] (e4) Vitamin complex 3rd mixing step

[0335] Technical reasons and critical significance of numerical range

[0336] The reason for setting the vitamin complex to 1.5-2.5% of the final composition is to ensure the minimum effective amount required for the expression of nutritional function while preventing side effects caused by excessive intake. Below 1.5%, the nutritional functional effect of the vitamin is negligible, and above 2.5%, there is concern about physiological imbalance due to excessive intake of water-soluble vitamins.

[0337] Since the vitamin complex is a trace component, it is very important to disperse it evenly. A stirring speed of 30-45 rpm is set with low shear force considering the heat sensitivity of the vitamins, and a mixing time of 10-15 minutes is sufficient time for complete dispersion of the trace components.

[0338] Specific implementation method

[0339] Before adding the vitamin complex, a small amount of crystalline cellulose is added to the existing mixture to prepare a dilution matrix. This is a pretreatment process to increase the dispersion efficiency of trace components. After passing the vitamin complex through a mesh sieve to remove aggregates, it is evenly fed over a period of 5 minutes using a vibrating feeder.

[0340] For the first 3 minutes of addition, mix at a low speed of 35 rpm to minimize heat loss of the vitamins. Then, increase the stirring speed to 40 rpm and mix continuously for 10 minutes. Monitor the mixer temperature during the mixing process to ensure it does not exceed 30℃, and activate the cooling system if necessary.

[0341] After mixing is complete, 8-point sampling is performed to check the uniformity of vitamin content. The content of vitamins B1, B2, and B6 in the samples is quantified through HPLC analysis, and it is confirmed that the relative standard deviation is within 5%.

[0342] (e5) Final homogenization mixing step

[0343] Technical reasons and critical significance of numerical range

[0344] The final homogenization step is a finishing process designed to achieve complete uniformity after all components have been added. The stirring speed of 60–80 rpm is intended to eliminate even minute non-uniformities by applying higher shear force than in the previous step. Exceeding 80 rpm raises concerns about particle destruction and static electricity generation due to excessive shear force, while speeds below 60 rpm result in insufficient homogenization.

[0345] A mixing time of 25–35 minutes is essential to achieve complete homogenization in large volumes. A particle size deviation of within ±10% is a quality standard to ensure the uniformity of the formulation's content and formulation stability. Visual inspection of color uniformity is a simple yet effective method for evaluating macroscopic uniformity.

[0346] Specific implementation method

[0347] After all ingredients have been added, inspect the inside of the mixer to check for wall deposits and residues in the dead space. Completely remove wall deposits using a scraper and resume stirring. Set the stirring speed to 70 rpm and perform final homogenization for 30 minutes.

[0348] During the homogenization process, stirring is paused every 10 minutes, and sampling is performed at 8 points. The color uniformity of the samples is visually checked, and the particle size distribution is measured using a particle size analyzer. Homogenization is continued until the particle size deviation reaches within ±10%.

[0349] The homogenization completion criterion is set when color uniformity is confirmed in two consecutive samples and there is no change in particle size distribution. After confirming that the temperature of the final mixture has returned to room temperature, proceed to the next step.

[0350] (e6) Foreign substance removal sorting step

[0351] Technical reasons and critical significance of numerical range

[0352] The reason for using a 150-200 mesh vibrator is to effectively remove foreign substances and aggregates that can affect product quality. Below 150 mesh, the removal of small foreign substances is incomplete, while above 200 mesh, even normal particles are removed, resulting in a decrease in yield. Double-pass screening is a measure to maximize screening efficiency and ensure the complete removal of foreign substances.

[0353] Vibrating screen separation is a physical separation method utilizing gravity and vibration that can remove foreign substances without chemical changes, thereby ensuring both product safety and purity.

[0354] Specific implementation method

[0355] Before use, clean the vibrator with compressed air and check for any damage to the mesh. Configure a two-stage screening system by arranging 150 mesh and 200 mesh units vertically. Set the vibration intensity to medium and adjust the vibration frequency to 50-60 Hz.

[0356] Sorting is started by slowly feeding the final homogenized mixture into the top of the vibrator. The feeding speed is adjusted to 80% of the vibrator's processing capacity to optimize sorting efficiency. After the first sorting is completed, the passed powder is collected, and a second sorting is performed under the same conditions.

[0357] Measure and record the amount of foreign substances and aggregates removed during the sorting process. If the foreign substance removal rate falls outside the expected range, analyze the issues in the previous process and implement corrective measures. Immediately collect the sorted powder in a sealed container to prevent contamination.

[0358] (e7) Moisture adjustment and homogeneity verification step

[0359] Technical reasons and critical significance of numerical range

[0360] A moisture content of 3.0% or less is an essential condition for ensuring the microbiological and chemical stability of the product. If it exceeds 3.0%, the risk of microbial growth increases and the decomposition of vitamins accelerates, while excessively low moisture content raises concerns regarding static electricity generation and reduced powder flowability. The loss-on-drying method is a standard method for measuring moisture content and offers excellent accuracy and reproducibility.

[0361] A vacuum drying temperature of 40-50℃ is a condition for achieving effective drying while minimizing the loss of heat-sensitive vitamins and active ingredients in plants. Observation of particle distribution using a 100x magnification microscope is a precise inspection to detect minute non-uniformities that are difficult to identify with the naked eye.

[0362] Specific implementation method

[0363] A representative sample of 5g is taken from the selected mixture, and the moisture content is measured using an infrared moisture meter. The accurate moisture content is reconfirmed using the loss on drying method at 105℃. If the moisture content exceeds 3.0%, additional drying is performed using a vacuum dryer.

[0364] Vacuum drying is performed under conditions of a vacuum of -0.08 MPa and a temperature of 45℃. The moisture content is measured every hour, and drying is continued until the target value is reached. After drying is complete, the mixture is cooled to room temperature and stored in an environment with a humidity of 30% or less.

[0365] Homogeneity is verified by sampling the mixture at eight points. After visually checking color uniformity, the particle distribution of each sample is observed using a 100x magnification optical microscope. Homogeneity is determined by comprehensively evaluating the uniformity of particle size and shape, the presence of foreign substances, and color deviation.

[0366] (e8) Stabilization and final composition completion stage

[0367] Technical reasons and critical significance of numerical range

[0368] A stabilization temperature of 15–20°C is the optimal condition for achieving physical stabilization between components and moisture equilibrium. Below 15°C, the stabilization rate decreases, and above 20°C, the risk of vitamin degradation increases. A stabilization time of 6–12 hours is essential for stabilizing interactions at the molecular level and relieving residual stress.

[0369] Physical stabilization among components is the process by which components with different physicochemical properties reach a stable equilibrium state. Achieving moisture equilibrium aims to minimize changes during product storage by balancing the moisture content of each component with the surrounding environment.

[0370] Specific implementation method

[0371] Fill the homogeneous mixture into a stainless steel airtight container. Before use, disinfect the container with ethanol and dry it completely. To minimize air pockets during filling, fill the container to 95% capacity and replace the headspace with nitrogen gas.

[0372] The filled container is transferred to a stabilization room and stored in an environment set at a temperature of 18±2℃ and a relative humidity of 40-50%. During the stabilization process, the container is gently rotated every 6 hours to prevent sedimentation. Temperature and humidity are continuously monitored using a data logger.

[0373] After stabilization is complete, a representative sample is taken for final quality verification and analyzed for appearance, color, odor, particle size distribution, moisture content, and major ingredient content. Once it is confirmed that all quality standards are met, the final composition is approved and transferred to the next process. The stabilized final composition is stored in an environment with a temperature of 15-25℃ and humidity of 60% or less to minimize the time to the formulation process.

[0374] The technical reasons, critical significance, and specific implementation methods of the above steps (f) and (f1) to (f8) are as follows.

[0375] (f) Overall overview of the step

[0376] The formulation step of the present invention is a key process for converting the final composition into a form that is easy to take orally and has excellent bioavailability. By providing three formulations—tablets, capsules, and granules—it is possible to satisfy the diverse preferences and convenience of consumption of consumers and ensure optimal release characteristics and stability for each formulation. Optimal conditions for each formulation were established by considering the stability and release characteristics of key active ingredients, such as cinafoside in Cynanchum wilfordii extract powder, ellagic acid in pomegranate concentrate powder, and the enzymatic activity of bromelain.

[0377] (f1) Tablet manufacturing process

[0378] Technical reasons and critical significance of numerical range

[0379] A compression pressure range of 8-15 kN using a tablet press is the optimal compression condition considering the physicochemical properties of the present composition. At low compression pressures of less than 8 kN, the compressibility of crystalline cellulose 102 is not sufficiently exhibited, resulting in insufficient mechanical strength of the tablet and an increased risk of breakage during transportation and storage. At excessive compression pressures exceeding 15 kN, the porosity inside the tablet decreases excessively, causing delayed disintegration, and in particular, the enzymatic activity of bromelain may be reduced by physical pressure.

[0380] A compression time of 2 to 5 seconds is the optimal condition for uniform tablet molding while minimizing the impact of heat and pressure generated during the compression process on the active ingredients. Rapid compression of less than 2 seconds may result in layer separation due to insufficient fluidity of the powder, and prolonged compression of more than 5 seconds may lead to thermal decomposition of cyanoside and ellagic acid due to frictional heat.

[0381] Specific implementation method

[0382] A rotary tablet press is used, and the punch and die are set to a circular or elliptical shape with a diameter of 8-10 mm. Before tableting, the moisture content of the final composition is adjusted to 3% or less, and the work is performed in an environment with a relative humidity of 40-50% to prevent static electricity. Pre-stirring is performed for 30 minutes before feeding the final composition into the hopper to prevent component separation.

[0383] The compression pressure starts at an initial 8 kN and is adjusted stepwise while measuring the tablet hardness. The compression time is controlled by adjusting the rotation speed of the tablet press, and is set so that the punch contact time is 2 to 5 seconds. During the tablet pressing process, the tablet weight and thickness are measured every 30 minutes to check process stability.

[0384] (f2) Refining Quality Control

[0385] Technical reasons and critical significance of numerical range

[0386] A tablet hardness of 5-12 kgf is the optimal range for balancing mechanical stability during packaging, transportation, and storage with disintegration upon administration. Hardness below 5 kgf causes the tablet to break easily, raising concerns about loss of active ingredients and dust generation within the packaging; conversely, excessive hardness exceeding 12 kgf delays disintegration in the gastrointestinal tract, thereby inhibiting the release and absorption of active ingredients.

[0387] A disintegration time of 15 to 30 minutes is the optimal release time considering the physiological characteristics of the gastrointestinal tract and the characteristics of the active ingredient of the present composition. Rapid disintegration of less than 15 minutes increases the risk of degradation of the active ingredient by gastric acid, while delayed disintegration of more than 30 minutes reduces the opportunity for absorption in the small intestine, thereby lowering bioavailability. In particular, appropriate release control is necessary because the enzymatic activity of bromelain can be affected by gastric acid.

[0388] Specific implementation method

[0389] Tablet hardness is measured by calculating the average value of 10 tablets using a hardness tester. If the hardness falls below the target range, the compression pressure is increased stepwise in increments of 1-2 kN, and if it exceeds the range, the compression pressure is decreased. After adjusting the hardness, production is continued for 30 minutes, and then re-measurement is performed to verify stability.

[0390] The disintegration time test is conducted in accordance with the disintegration test method of the Korean Pharmacopoeia. Purified water is used as the test solution, and the test is performed at a temperature of 37±2℃. Six tablets are tested, and the time for all tablets to completely disintegrate is measured. If the disintegration time falls outside the range, the content of crystalline cellulose 102 or the compression conditions are readjusted.

[0391] (f3) Capsule manufacturing process

[0392] Technical reasons and critical significance of numerical range

[0393] The selection of hard gelatin capsule No. 0 or No. 1 using an automatic capsule filler is made considering the bulk density of the final composition and the single dose. A filling amount of 500-800 mg is the optimal range set based on the content of the active ingredient in the composition and the recommended daily intake. If the amount is less than 500 mg, multiple capsules must be taken to ensure sufficient intake of the active ingredient, which reduces convenience of administration, and if it exceeds 800 mg, the capsule size becomes excessive, which may cause dysphagia.

[0394] The use of hard gelatin capsules is a choice made to optimize the stability and release characteristics of the active ingredient. Since gelatin capsules rapidly dissolve in gastric acid to release their contents, they are advantageous for preserving the enzymatic activity of bromelain and ensuring the rapid absorption of cynafoside.

[0395] Specific implementation method

[0396] The automatic capsule filling machine uses a tamping pin method, and less than 2% of magnesium stearate may be added to improve the fluidity of the final composition before filling. Before capsule filling, the relative humidity is adjusted to 45-55% in a humidity control room to prevent brittleness of the gelatin capsules.

[0397] The filling amount is controlled by adjusting the filling depth and tamping pressure. The standard is set to 700-800 mg for Capsule No. 0 and 500-600 mg for Capsule No. 1. Process stability is monitored by weighing 10 randomly selected capsules every 10 minutes during the filling process. Capsule sealing is performed using an automatic sealing machine at a constant pressure, and the sealing strength is adjusted to ensure the capsule does not easily detach while rapidly dissolving in the gastrointestinal tract upon administration.

[0398] (f4) Capsule Quality Control

[0399] Technical reasons and critical significance of numerical range

[0400] The standard of a capsule weight deviation of within ±5% is a pharmaceutical industry standard designed to ensure content uniformity and dosage accuracy. Weight deviations exceeding ±5% lead to reduced consistency in therapeutic efficacy due to non-uniformity in the active ingredient content; in particular, for ingredients with a narrow effective concentration range, such as cyanoside, the variation in efficacy may be significant.

[0401] Visual inspection of the seal is an essential process to verify the physical integrity of the capsule and the protection of its contents. Incomplete sealing increases the risk of degradation of the active ingredient due to moisture penetration and microbial contamination.

[0402] Specific implementation method

[0403] Weight deviation management involves randomly selecting 20 capsules every hour during the production process and measuring them with a precision scale. If the weight of an individual capsule falls outside the ±5% range of the average value, the tamping pressure and filling depth of the filler are readjusted. If the value falls outside the range in three consecutive measurements, production is stopped and the cause is analyzed.

[0404] Visual inspection of the sealing condition is performed by a skilled inspector who visually checks the sealing status, cracks, deformation, etc. of the capsules. The inspection is conducted under white light with an illuminance of 500 lux or higher, and if a defective capsule is found, the entire batch is re-inspected. If the sealing failure rate exceeds 0.1%, the sealing pressure is readjusted.

[0405] (f5) Granule manufacturing process

[0406] Technical reasons and critical significance of numerical range

[0407] Granulation using a fluidized bed granulator is a process for improving the fluidity of the final composition and preventing component separation. An inlet temperature of 60-80°C is the optimal temperature for activating components that act as binders and for moisture evaporation. Below 60°C, granule formation is insufficient, raising concerns about dust generation and component separation, while above 80°C, the enzymatic activity of heat-sensitive bromelain and the stability of cynafoside may be impaired.

[0408] An exhaust temperature of 40-50℃ is the balance point between moisture removal efficiency and protection of active ingredients. A spray pressure of 1-3 bar is a condition for uniform granule formation and proper moisture supply; below 1 bar, spray efficiency decreases, and above 3 bar, aggregation may occur due to excessive moisture supply.

[0409] Specific implementation method

[0410] The fluidized bed granulator uses a batch type, and the input volume is set to 70-80% of the equipment capacity. A 2-3% aqueous solution of hydroxypropylcellulose is used as a binder, and the spray speed is adjusted while observing the fluidity of the powder layer. At the beginning of the process, the inlet temperature is set low to preheat the powder, and then gradually raised to the target temperature.

[0411] The granulation process proceeds in three stages. In the first stage, only preheating is performed without spraying; in the second stage, granules are formed while spraying a binder; and in the third stage, spraying is stopped and drying is completed. The temperature, pressure, and flow rate of each stage are monitored in real time, and drying is continued until the moisture content of the granules reaches the target range.

[0412] (f6) Granule Quality Control

[0413] Technical reasons and critical significance of numerical range

[0414] A granule particle size of 14-30 mesh is the range for optimizing tablet performance and fluidity. With coarse granules larger than 14 mesh, wear on the punch and die increases during tablet compression and roughness of the tablet surface occurs, while with fine granules smaller than 30 mesh, there is a concern about increased weight variation and dust generation due to reduced fluidity.

[0415] A moisture content of 2-4% is a condition for simultaneously ensuring the physical stability of the granules and the chemical stability of the active ingredient. In an excessively dry state of less than 2%, the brittleness of the granules increases, leading to dust generation, while in a high moisture content exceeding 4%, there is a risk of microbial growth and the hydrolysis reaction of the active ingredient may be accelerated.

[0416] Specific implementation method

[0417] Particle size adjustment is performed by combining sieving with a vibrating screen and grinding with a hammer mill. Coarse granules that do not pass through a 30-mesh screen are ground with a hammer mill, while fine granules that pass through a 14-mesh screen are collected separately and re-granulated. Sieving and grinding are repeated until at least 85% of the granules fall within the target particle size range.

[0418] Moisture content is measured using an infrared moisture meter and verified by the loss on drying method at 105°C. If the moisture content exceeds 4%, additional drying is performed in a fluidized bed dryer, and if it is less than 2%, an appropriate amount of moisture is supplied using a dehumidifier. After adjusting the moisture content, the product is stabilized in a sealed container for 24 hours to check the moisture equilibrium state.

[0419] (f7) Packaging process

[0420] Technical reasons and critical significance of numerical range

[0421] The selection of aluminum-PTP packaging and HDPE containers is based on considerations of formulation characteristics and the stability of the active ingredient. Aluminum-PTP packaging is optimized for tablets and provides excellent light-blocking and moisture-proof properties, preventing photodegradation and oxidation of cyanoside and ellagic acid. HDPE containers are suitable for capsules and granules and offer excellent chemical resistance, which is advantageous for maintaining the enzymatic activity of bromelain.

[0422] The selection of packaging by dosage form considers both storage stability and ease of use. While tablets require individual packaging, bulk packaging is economical and practical for capsules and granules.

[0423] Specific implementation method

[0424] Aluminum-PTP packaging utilizes a blister packaging machine and uses packaging materials with an aluminum thickness of 20㎛ or more. Prior to packaging, the material is pretreated in an environment with a relative humidity of 40% or less, and the heat sealing temperature is set to 160-180℃. During the packaging process, internal air is removed through vacuum treatment, and nitrogen purging is performed to prevent oxidation.

[0425] HDPE container packaging is performed using an automatic filling machine, and the containers are washed with ethanol and dried before use. After filling, desiccant is inserted, and the container is first sealed with an induction seal and then secondarily sealed with a cap. The packaged product is immediately stored in a light-shielding outer packaging material.

[0426] (f8) Storage and Quality Control

[0427] Technical reasons and critical significance of numerical range

[0428] A storage temperature of 15-25°C and a relative humidity of 60% or less are conditions to ensure the long-term stability of the active ingredient. Above 25°C, the decomposition reaction of cynafoside is accelerated and the enzymatic activity of bromelain decreases, while below 15°C, there is a concern regarding changes in physical properties due to crystallization. Above 60% relative humidity, the risk of ingredient decomposition due to hygroscopicity and microbial growth increases.

[0429] Quality control items such as appearance, weight, uniformity of content, disintegration test, and microbiological test are essential for comprehensively evaluating the safety and efficacy of a product. Through these tests, changes in quality during storage can be monitored and the shelf life can be set.

[0430] Specific implementation method

[0431] The storage room is equipped with temperature and humidity control facilities and monitors temperature and humidity data loggers 24 hours a day. Stored products are placed on pallets at least 10 cm above the floor and at least 50 cm away from the walls to ensure air circulation.

[0432] Quality control is conducted at 1, 3, 6, and 12 months of storage. Visual inspection involves checking color, shape, and foreign matter visually, while weight measurement involves determining the average weight of individual formulations using a precision balance. Content uniformity testing quantifies the content of major active ingredients using HPLC, and disintegration testing is performed in accordance with the Korean Pharmacopoeia methods. Microbiological testing confirms compliance with microbial limit test standards by measuring total bacterial counts, fungal counts, and coliforms.

[0433] In addition, the present invention relates to an oral food composition for improving female breast volume and gynecomastia and improving beauty through the regulation of estrogen / progesterone balance and the promotion of collagen synthesis, wherein the oral food composition for improving female breast volume and gynecomastia and improving beauty through the regulation of estrogen / progesterone balance and the promotion of collagen synthesis is manufactured by a method for manufacturing said oral food composition.

[0434] Hereinafter, the structure of the present invention and the resulting effects are to be explained in more detail through specific embodiments and comparative examples. However, these embodiments are intended to explain the present invention more specifically, and the scope of the present invention is not limited to these embodiments.

[0435] Example 1

[0436] 5.0 parts by weight of Cynanchum wilfordii extract powder were prepared, standardized by HPLC to a cyanoside content of 0.30 wt%, and dried at 45°C for 36 hours. 57.5 parts by weight of pomegranate concentrate powder were standardized to an ellagic acid content of 5.0 wt% and stored at 20°C and 12% humidity. 10.0 parts by weight of Sophora japonica fruit extract powder were standardized to a rutin content of 10.0 wt% and ground to 100 mesh, and 10.0 parts by weight of soybean extract powder were standardized to an isoflavone content of 25.0 wt% and ground to 100 mesh. 5.0 parts by weight of bromelain powder were adjusted by spectrophotometry to an enzyme activity of 2500 GDU / g and refrigerated at 4°C. 5.0 parts by weight of crystalline cellulose 102, 0.35 parts by weight of vitamin B1 hydrochloride, 0.30 parts by weight of vitamin B2, 0.40 parts by weight of vitamin B6 hydrochloride, and 0.45 parts by weight of vitamin B12 were each prepared.

[0437] After pre-treating Cynanchum wilfordii extract powder at 30°C for 3 hours, a plant extract mixture was prepared by sequentially mixing Sophora japonica fruit extract powder and soybean extract powder. A functional mixture was prepared by mixing pomegranate concentrate powder and bromelain powder in a weight ratio of 12:1, and a vitamin complex was prepared by mixing vitamins B1, B2, B6, and B12 in a weight ratio of 1:0.94:1.23:0.16. A final composition was prepared by sequentially mixing the plant extract mixture, the functional mixture, and the vitamin complex with crystalline cellulose 102.

[0438] Tablets were manufactured from the final composition using a tablet press under conditions of a compression pressure of 12 kN and a compression time of 3 seconds. The hardness of the manufactured tablets was 8.5 kgf and the disintegration time was 22 minutes.

[0439] Example 2

[0440] 7.0 parts by weight of Cynanchum wilfordii extract powder were standardized to a cyanoside content of 0.25 wt%, and 50.0 parts by weight of pomegranate concentrate powder were standardized to an ellagic acid content of 5.5 wt%. 12.0 parts by weight of Sophora japonica fruit extract powder were standardized to a rutin content of 9.0 wt%, and 12.0 parts by weight of soybean extract powder were standardized to an isoflavone content of 28.0 wt%. 7.0 parts by weight of bromelain powder were adjusted to an enzyme activity of 2800 GDU / g, and 7.0 parts by weight of crystalline cellulose 102, 0.30 parts by weight of vitamin B1 hydrochloride, 0.25 parts by weight of vitamin B2, 0.35 parts by weight of vitamin B6 hydrochloride, and 0.40 parts by weight of vitamin B12 were prepared.

[0441] Each raw material was pretreated in the same manner as in Example 1, and a final composition was prepared through stepwise mixing. Then, capsules were manufactured by filling 650 mg into No. 0 hard gelatin capsules using an automatic capsule filler. The weight deviation of the capsules was managed within ±3.2%.

[0442] Comparative Example 1

[0443] Excluding Cynanchum wilfordii extract powder, the composition consisted of 62.5 parts by weight of pomegranate concentrate powder, 10.0 parts by weight of Sophora japonica fruit extract powder, 10.0 parts by weight of soybean extract powder, 5.0 parts by weight of bromelain powder, 5.0 parts by weight of crystalline cellulose 102, 0.35 parts by weight of vitamin B1 hydrochloride, 0.30 parts by weight of vitamin B2, 0.40 parts by weight of vitamin B6 hydrochloride, and 0.45 parts by weight of vitamin B12. The standardization conditions and manufacturing methods for each raw material were applied in the same manner as in Example 1.

[0444] Comparative Example 2

[0445] It was composed of 5.0 parts by weight of Cynanchum wilfordii extract powder, 30.0 parts by weight of pomegranate concentrate powder, 10.0 parts by weight of Sophora japonica fruit extract powder, 10.0 parts by weight of soybean extract powder, 5.0 parts by weight of bromelain powder, 5.0 parts by weight of crystalline cellulose 102, 2.5 parts by weight of vitamin B complex, and 32.5 parts by weight of corn starch. The content of pomegranate concentrate powder was set to less than 50 parts by weight and compared with the range of the present invention.

[0446] Comparative Example 3

[0447] The composition was prepared by adding 5.0 parts by weight of Cynanchum wilfordii extract powder, 62.5 parts by weight of pomegranate concentrate powder, 10.0 parts by weight of Sophora japonica fruit extract powder, 10.0 parts by weight of soybean extract powder, 5.0 parts by weight of crystalline cellulose 102, 0.35 parts by weight of vitamin B1 hydrochloride, 0.30 parts by weight of vitamin B2, 0.40 parts by weight of vitamin B6 hydrochloride, and 0.45 parts by weight of vitamin B12, excluding bromelain powder. The remaining manufacturing conditions were applied in the same manner as in Example 1.

[0448] Measurement of antioxidant activity

[0449] The compositions prepared in each example and comparative example were extracted using methanol. 1 g of the composition was added to 100 mL of methanol and extracted by shaking at room temperature for 24 hours, then filtered to obtain the extract. Sample solutions were prepared by diluting the extracts to different concentrations.

[0450] The DPPH radical scavenging activity was measured as follows. A 0.1 mM DPPH solution was prepared by dissolving it in methanol, and 0.2 mL of the sample solution was mixed with 1.8 mL of the DPPH solution and reacted at room temperature for 30 minutes. After the reaction, the absorbance was measured at 517 nm using a spectrophotometer. Methanol was used as the control, and ascorbic acid was used as the positive control.

[0451] ABTS radical scavenging activity was measured by preparing an ABTS cation radical solution, reacting it with the sample solution, and measuring the absorbance at 734 nm. Each experiment was repeated three times to obtain the average value, and the radical scavenging activity was calculated using the following formula.

[0452] Radical scavenging activity (%) = [(Control absorbance - Sample absorbance) / Control absorbance] × 100

[0453] Sample Concentration (mg / mL) DPPH Scavenging Activity (%) ABTS elimination ability (%) Example 1 1.0 78.5 ± 2.1 82.3 ± 1.8 Example 2 1.0 75.2 ± 1.9 79.8 ± 2.2 Comparative Example 1 1.0 65.3 ± 2.5 68.7 ± 2.0 Comparative Example 2 1.0 52.1 ± 3.1 55.4 ± 2.8 Comparative Example 3 1.0 71.2 ± 2.3 74.5 ± 1.9 Ascorbic acid 0.1 95.8 ± 0.8 97.2 ± 0.5

[0454] As a result of measuring antioxidant activity, Examples 1 and 2 of the present invention showed significantly superior antioxidant activity compared to all comparative examples. In the case of Example 1, the DPPH radical scavenging activity was the highest at 78.5%, and the ABTS radical scavenging activity also showed excellent results at 82.3%.

[0455] Comparative Example 1, in which the Cynanchum wilfordii extract powder was excluded, showed approximately 13-17% lower antioxidant activity compared to the example, confirming that the cyanoside component of the Cynanchum wilfordii extract powder plays an important role in enhancing the antioxidant activity of the entire composition. Comparative Example 2, in which the pomegranate concentrate powder content was less than 50 parts by weight, showed significantly lower antioxidant activity, proving that the optimal content of pomegranate concentrate powder is decisive for the antioxidant effect.

[0456] Comparative Example 3, which excluded bromelain powder, showed slightly lower antioxidant activity compared to the Example, but higher results than Comparative Examples 1 and 2. This suggests that bromelain plays a role in indirectly enhancing the overall effect by improving the bioavailability of other active ingredients rather than direct antioxidant activity.

Claims

Claim 1 A method for preparing an orally ingestible food composition for improving female breast volume, alleviating gynecomastia, and enhancing beauty by regulating estrogen / progesterone balance and promoting collagen synthesis, comprising: 3-7 parts by weight of Cynanchum wilfordii Hemsley extract powder, 50-65 parts by weight of pomegranate concentrate powder, 8-12 parts by weight of Sophora japonica fruit extract powder, 8-12 parts by weight of soybean extract powder, 3-7 parts by weight of bromelain powder, 3-7 parts by weight of crystalline cellulose 102, 0.2-0.5 parts by weight of vitamin B1 (hydrochloride), 0.2-0.4 parts by weight of vitamin B2, 0.3-0.5 parts by weight of vitamin B6 hydrochloride, and 0.3-0.6 parts by weight of vitamin B12, wherein (a) 3-7 parts by weight of Cynanchum wilfordii Hemsley extract powder, 50-65 parts by weight of pomegranate concentrate powder (a) a step of preparing raw materials comprising parts by weight of Sophora japonica fruit extract powder, 8-12 parts by weight of soybean extract powder, 3-7 parts by weight of bromelain powder, 3-7 parts by weight of crystalline cellulose 102, 0.2-0.5 parts by weight of vitamin B1 (hydrochloride), 0.2-0.4 parts by weight of vitamin B2, 0.3-0.5 parts by weight of vitamin B6 hydrochloride, and 0.3-0.6 parts by weight of vitamin B12; (b) a step of preparing a plant extract mixture by mixing the above Cynanchum wilfordii extract powder, the above Sophora japonica fruit extract powder, and the above soybean extract powder; (c) a step of preparing a functional mixture by mixing the above pomegranate concentrate powder and the above bromelain powder; (d) a step of preparing a vitamin complex by mixing the above vitamin B1 (hydrochloride), the above vitamin B2, the above vitamin B6 hydrochloride, and the above vitamin B12; (e) the above A step of preparing a final composition by sequentially mixing a plant extract mixture, the functional mixture, the vitamin complex, and the crystalline cellulose 102; (f) a step of molding the final composition into a form suitable for oral intake; wherein step (a) comprises a Cynanchum wilfordii extract powder with a cyanoside content of 0.2-0.The step involves standardizing to 4 wt%, standardizing pomegranate concentrate powder to an ellagic acid content of 4-6 wt%, Sophora japonica fruit extract powder to a rutin content of 8-12 wt%, and soybean extract powder to an isoflavone content of 20-30 wt% by HPLC, adjusting the enzymatic activity of bromelain powder to 2000-3000 GDU / g, and confirming and quantifying the purity of vitamins B1, B2, B6, and B12; and the above step (b) involves pre-treating Cynanchum wilfordii extract powder at a temperature of 25-35℃, wetting Sophora japonica fruit extract powder with purified water, and antioxidantizing soybean extract powder with nitrogen gas, then sequentially mixing them, undergoing first and second mixing, drying and homogenizing at a temperature of 40-60℃, and then aging at a temperature of 20-25℃ for 45-60 minutes. The step involves preparing a plant extract mixture; the above step (c) involves pre-treating pomegranate concentrate powder at a temperature of 28-32℃ and standardizing the enzyme activity of bromelain powder to 2200-2800 GDU / g, then mixing the pomegranate concentrate powder and bromelain powder in a weight ratio of 11:1-13:1 in a V-type mixer, adding ascorbic acid as an antioxidant for enzyme stabilization treatment, and then aging the mixture for 30-42 hours in a nitrogen-substituted sealed container to prepare a functional mixture; and the above step (d) involves confirming the purity of vitamins B1, B2, and B6 to be 78%, 100%, and 82% or higher, respectively, and diluting vitamin B12 to 1.0% or higher, then first mixing the water-soluble vitamins in a weight ratio of 1:0.94±0.05:1.23±0.05, and adding the diluted vitamin B12 in a ratio of 1:0.16±0.02 The step of preparing a vitamin complex involves adding by weight ratio, performing a second mixing, sieving through a 200-300 mesh sieve, and stabilizing at 10-20℃; the above step (e) involves pre-stirring crystalline cellulose 102 in a large-capacity mixer, then sequentially adding the plant extract mixture at 15-25% of the target weight of the final composition, the functional mixture at 60-70%, and the vitamin complex at 1.5-2.5% while performing first, second, and third mixing respectively, finally homogenizing, and then sieving through a 150-200 mesh to obtain a moisture content of 3.A method for preparing an oral food composition for improving female breast volume and gynecomastia, and improving beauty through the regulation of estrogen / progesterone balance and promotion of collagen synthesis, characterized by the step of preparing a final composition by adjusting and stabilizing it to 0% or less, and the step (f) being the step of preparing tablets by pressing the final composition at a compression pressure of 8-15 kN, preparing capsules by filling 500-800 mg into hard gelatin capsules, or preparing granules by using a fluid bed granulator at an inlet temperature of 60-80℃, then adjusting the particle size and moisture content of each formulation, packaging them in aluminum-PTP packaging or HDPE containers, and storing them under quality control at a temperature of 15-25℃. 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