Production method of composition for reversing insulin resistance

Abstract

The invention relates to the technical field of insulin resistance reversing, in particular to a production method of a composition for reversing insulin resistance, which comprises the following steps: crushing and sieving a kudzuvine root extract, a coptis chinensis extract, a cinnamon extract and a mulberry leaf extract; the extract raw materials are put into a three-dimensional motion mixer to be mixed, and a uniform plant extract mixture is obtained; the preparation method comprises the following steps: dispersing chromium picolinate and absolute ethyl alcohol in a shearing dispersion machine to prepare slurry, and meanwhile, carrying out equivalent incremental dilution and premixing on L-carnitine and microcrystalline cellulose to obtain a premix; jointly putting the plant extract mixture, the slurry and the premix into a high-efficiency wet granulator, adding purified water as an adhesive, and granulating to obtain wet granules; drying the wet particles in a boiling drying bed, and then carrying out vibration screening to obtain uniform dry particles; and mixing the dry particles with magnesium stearate, pressing the mixture into tablet cores, and coating the tablet cores. The production efficiency of the composition for reversing insulin resistance is improved.

Description

Technical Field

[0001] This invention relates to the field of insulin resistance reversal technology, and more particularly to a method for producing an insulin resistance reversal composition. Background Technology

[0002] Insulin resistance is a common pathological basis and core component of many major metabolic diseases, including type 2 diabetes, metabolic syndrome, and non-alcoholic fatty liver disease. It is characterized by decreased sensitivity of peripheral tissues (such as skeletal muscle, liver, and fat) to insulin, resulting in insufficient physiological effects from normal insulin concentrations. This forces pancreatic β-cells to compensate by secreting excessive insulin, leading to hyperinsulinemia. Without intervention, this compensatory mechanism eventually fails, resulting in overt hyperglycemia and a series of serious complications.

[0003] Currently, clinical interventions for insulin resistance primarily rely on lifestyle management (such as diet control and exercise) and drug therapy. While mainstream drugs like metformin and thiazolidinediones can improve insulin sensitivity to some extent, they have side effects such as gastrointestinal reactions, weight gain, edema, increased risk of fractures, and even potential cardiovascular risks, limiting their long-term and widespread use. Therefore, developing safe, effective solutions derived from natural products has become a current research hotspot.

[0004] Chinese Patent Application Publication No. CN120549962A discloses a composition containing components that reverse insulin resistance and its preparation method. The composition includes quercetin, proanthocyanidins, malic acid, magnesium carbonate, zinc lactate, and cereals. Through the synergistic effect of each component, it can reduce fasting blood glucose, fasting insulin, and insulin resistance index, and improve insulin sensitivity index. This overcomes the problems of complex composition of traditional Chinese medicine compositions in the prior art, unclear effective components and synergistic mechanisms that can reverse insulin resistance, and inconsistent content of effective components in the same drug due to the influence of the growth environment, which leads to unpredictable therapeutic effects.

[0005] However, the existing technology has the following problems: the existing traditional Chinese medicine compositions for reversing insulin resistance have complex components and unclear effective components, and their synergistic mechanism lacks scientific verification; at the same time, the content of effective components in natural medicines is significantly affected by the growth environment, resulting in unpredictable therapeutic effects and poor stability of different batches of drugs, making it difficult to achieve standardized production and precision treatment. Summary of the Invention

[0006] Therefore, the present invention provides a method for producing a composition to reverse insulin resistance, thereby overcoming the problems in the prior art where the content of the active ingredients in natural drugs is affected by the growth environment, resulting in unstable efficacy between batches and difficulty in achieving standardized production.

[0007] To achieve the above objectives, the present invention provides a method for producing a composition for reversing insulin resistance, comprising: Step S1, prepare the raw materials including: kudzu root extract, coptis extract, cinnamon extract, mulberry leaf extract, chromium pyridinecarboxylate and L-carnitine; Step S2: Crush and sieve the raw materials of each extract, and use high performance liquid chromatography to determine whether the content of key active ingredients in the raw materials meets the preset standards. The key active ingredients include puerarin, berberine, cinnamon polyphenols and DNJ. Step S3: If the content of the key active ingredient does not meet the preset standard, dynamically adjust the actual weight of each raw material within the weight ratio range of the key active ingredient. Step S4: Add the determined actual weights of kudzu root extract, coptis root extract, cinnamon extract, and mulberry leaf extract into a three-dimensional motion mixer and mix to obtain a uniform mixture of plant extracts. Step S5: Chromium pyridinecarboxylate and anhydrous ethanol are dispersed in a shear disperser to form a slurry, while L-carnitine and microcrystalline cellulose are diluted and premixed in equal increments to obtain a premix. Step S6: The plant extract mixture, slurry and premix are fed into a high-efficiency wet granulator, purified water is added as a binder and then granulated to obtain wet granules. Step S7: Determine the average particle size of the wet particles using a laser particle size analyzer, and determine the passability of the granulation process based on the average particle size. If the passability is not met, reduce the rate of adding the binder. Step S8: Under the condition that the granulation process is qualified, the wet granules are dried in a fluidized bed dryer and then oscillated and screened to obtain uniform dry granules. Step S9: After mixing the dry granules with magnesium stearate, the mixture is pressed into tablet cores using a high-speed tablet press, and then coated with a film coating premix in a high-efficiency coating pan.

[0008] Furthermore, the raw materials are composed of the following parts by weight: 10-30 parts of kudzu root extract, 5-15 parts of coptis root extract, 3-10 parts of cinnamon extract, 8-20 parts of mulberry leaf extract, 0.1-0.5 parts of chromium pyridinecarboxylate, and 2-8 parts of L-carnitine.

[0009] Furthermore, the content standards for key active ingredients in step S2 include: The content of puerarin in kudzu root extract is greater than or equal to the first preset content; The berberine content in Coptis chinensis extract is greater than or equal to the second preset content; The cinnamon polyphenol content in the cinnamon extract is greater than or equal to the third preset content; The DNJ content in mulberry leaf extract is greater than or equal to the fourth preset content.

[0010] Furthermore, the kudzu root extract, coptis root extract, cinnamon extract, and mulberry leaf extract are all obtained by water extraction and alcohol precipitation or ultrasound-assisted extraction, and are obtained as powdered extracts by spray drying.

[0011] Furthermore, the weight ratio of the key active ingredients in step S3 is as follows: 8-12 parts of puerarin, 2.5-4 parts of berberine, 0.6-1.2 parts of cinnamon polyphenols, and 0.16-0.24 parts of DNJ.

[0012] Furthermore, in step S7, if the average particle size is greater than or equal to the preset particle size, the granulation process is deemed unqualified, and the addition rate of the adhesive is reduced based on the difference between the average particle size and the preset particle size.

[0013] Furthermore, the drying process employs near-infrared spectroscopy technology to monitor particle moisture content online in real time, and automatically stops drying when the detected moisture content reaches a preset level.

[0014] Furthermore, the film coating premix is ​​a stomach-soluble Opadry, the coating solution concentration is 12-15%, the inlet air temperature of the coating pan is controlled at 60-70℃, and the tablet bed temperature is maintained at 38-42℃.

[0015] Compared with existing technologies, the beneficial effects of this invention are that it introduces a step of detecting the content of key active ingredients in raw materials before feeding, and makes dynamic adjustments to the feeding based on this. This overcomes the problem of component fluctuations in natural drug raw materials caused by differences in growth environment. By performing reverse calculation and compensation with the fixed proportion of active ingredients in the final product as the target, it ensures that the chemical basis of each batch of products is consistent, thereby guaranteeing the reliability and reproducibility of the therapeutic effect.

[0016] Furthermore, this invention introduces an online monitoring and feedback control mechanism at the two key stages of granulation and drying. A laser particle size analyzer monitors the wet particle size in real time and automatically adjusts the binder addition rate, effectively preventing excessively fine particles or clumping, ensuring particle size uniformity, and guaranteeing the smooth progress of subsequent tableting and coating. In the drying step, near-infrared spectroscopy is used to monitor moisture content online and automatically determine the endpoint, replacing the traditional, time-consuming, and inaccurate sampling and testing methods that rely on manual experience. This avoids under-drying or over-drying, further improving product quality uniformity and production efficiency. Attached Figure Description

[0017] Figure 1 This is a flowchart of a method for producing the insulin resistance reversal composition according to an embodiment of the present invention; Figure 2 This is a flowchart illustrating how the granulation process is judged based on average particle size according to an embodiment of the present invention. Detailed Implementation

[0018] To make the objectives and advantages of the present invention clearer, the present invention will be further described below with reference to embodiments; it should be understood that the specific embodiments described herein are merely for explaining the present invention and are not intended to limit the present invention.

[0019] Preferred embodiments of the present invention will now be described with reference to the accompanying drawings. Those skilled in the art should understand that these embodiments are merely illustrative of the technical principles of the present invention and are not intended to limit the scope of protection of the present invention.

[0020] It should be noted that the data in this embodiment are all derived from a comprehensive analysis and evaluation of historical test data and corresponding historical test results from the three months prior to this test. Those skilled in the art will understand that the determination of the above-mentioned parameters for any single item in this invention can be achieved by selecting the value with the highest percentage based on the data distribution as the preset standard parameter, using weighted summation to obtain the value as the preset standard parameter, substituting each historical data point into a specific formula and using the value obtained from that formula as the preset standard parameter, or other selection methods, as long as the invention can clearly define different specific situations in the single-item judgment process through the obtained values.

[0021] Please see Figure 1 , Figure 2 The flowcharts shown are respectively a production method of the insulin resistance reversal composition according to an embodiment of the present invention; and a flowchart of determining the qualification of the granulation process based on the average particle size according to an embodiment of the present invention.

[0022] The present invention provides a method for producing a composition that reverses insulin resistance, comprising: Step S1, prepare the raw materials including: kudzu root extract, coptis extract, cinnamon extract, mulberry leaf extract, chromium pyridinecarboxylate and L-carnitine; Step S2: Crush and sieve the raw materials of each extract, and use high performance liquid chromatography to determine whether the content of key active ingredients in the raw materials meets the preset standards. The key active ingredients include puerarin, berberine, cinnamon polyphenols and DNJ. Step S3: If the content of the key active ingredient does not meet the preset standard, dynamically adjust the actual weight of each raw material within the weight ratio range of the key active ingredient. Step S4: Add the determined actual weights of kudzu root extract, coptis root extract, cinnamon extract, and mulberry leaf extract into a three-dimensional motion mixer and mix to obtain a uniform mixture of plant extracts. Step S5: Chromium pyridinecarboxylate and anhydrous ethanol are dispersed in a shear disperser to form a slurry, while L-carnitine and microcrystalline cellulose are diluted and premixed in equal increments to obtain a premix. Step S6: The plant extract mixture, slurry and premix are fed into a high-efficiency wet granulator, purified water is added as a binder and then granulated to obtain wet granules. Step S7: Determine the average particle size of the wet particles using a laser particle size analyzer, and determine the passability of the granulation process based on the average particle size. If the passability is not met, reduce the rate of adding the binder. Step S8: Under the condition that the granulation process is qualified, the wet granules are dried in a fluidized bed dryer and then oscillated and screened to obtain uniform dry granules. Step S9: After mixing the dry granules with magnesium stearate, the mixture is pressed into tablet cores using a high-speed tablet press, and then coated with a film coating premix in a high-efficiency coating pan.

[0023] Specifically, the ingredients are composed of the following parts by weight: 10-30 parts of kudzu root extract, 5-15 parts of coptis root extract, 3-10 parts of cinnamon extract, 8-20 parts of mulberry leaf extract, 0.1-0.5 parts of chromium pyridinecarboxylate, and 2-8 parts of L-carnitine.

[0024] Specifically, the key active ingredient content standards in step S2 include: The content of puerarin in kudzu root extract is greater than or equal to the first preset content; The berberine content in Coptis chinensis extract is greater than or equal to the second preset content; The cinnamon polyphenol content in the cinnamon extract is greater than or equal to the third preset content; The DNJ content in mulberry leaf extract is greater than or equal to the fourth preset content.

[0025] In this embodiment of the invention, the first preset content is 40% (w / w), the second preset content is 50% (w / w), the third preset content is 20% (w / w), and the fourth preset content is 2% (w / w).

[0026] Specifically, the kudzu root extract, coptis root extract, cinnamon extract, and mulberry leaf extract are all obtained by water extraction and alcohol precipitation or ultrasound-assisted extraction, and are obtained as powdered extracts by spray drying.

[0027] Specifically, step S3 dynamically adjusts the actual weight of each raw material using the following formula: Actual weight = (Theoretical weight × Standard content of key active ingredients) / Measured content.

[0028] Specifically, in step S4, kudzu root extract, coptis root extract, cinnamon extract and mulberry leaf extract are added to a three-dimensional motion mixer and mixed at 12-18 rpm for 45-60 minutes to obtain a uniform mixture of plant extracts.

[0029] Specifically, in step S5, chromium pyridinecarboxylate and an equal weight of anhydrous ethanol are dispersed in a shear disperser at 3000 rpm for 5 minutes.

[0030] Specifically, in step S6, the plant extract mixture, slurry, and premix are fed into a high-efficiency wet granulator, and 8%-12% of purified water by weight of the total composition is added as a binder. Granulation is carried out under the conditions of a stirring paddle speed of 200 rpm and a chopping blade speed of 1500 rpm to obtain wet granules.

[0031] Specifically, in step S7, the wet particles are dried in a fluidized bed at 55-65°C until the moisture content of the particles is less than 5.0%, and then granulated by a vibrating sieve to obtain uniform dry particles of 20-40 mesh.

[0032] Specifically, the weight ratio of the key active ingredients in step S3 is as follows: 8-12 parts of puerarin, 2.5-4 parts of berberine, 0.6-1.2 parts of cinnamon polyphenols, and 0.16-0.24 parts of DNJ.

[0033] Specifically, in step S7, if the average particle size is greater than or equal to the preset particle size, the granulation process is deemed unqualified, and the addition rate of the adhesive is reduced based on the difference between the average particle size and the preset particle size; if the average particle size is less than the preset particle size, the granulation process is deemed qualified.

[0034] Specifically, if the particle size difference is less than the preset difference, the addition rate of the adhesive is reduced to the corresponding value using the first rate adjustment coefficient of 0.85. If the particle size difference is greater than or equal to the preset difference, the addition rate of the adhesive is reduced to the corresponding value using the second rate adjustment coefficient of 0.7. The particle size difference is the difference between the average particle size and the preset particle size.

[0035] In this embodiment of the invention, the preset particle size is 250 μm, the preset difference is 50 μm, and the initial adhesive addition rate is 300 mL / min. However, the above values ​​are not limited to these values, and those skilled in the art can adjust the above values ​​according to actual needs.

[0036] Specifically, the drying process uses near-infrared spectroscopy to monitor the moisture content of the particles in real time online. When the moisture content reaches a preset level, the drying process automatically stops.

[0037] In this embodiment of the invention, the preset content is 4.5% ± 0.5%.

[0038] Specifically, the film coating premix is ​​gastrointestinal soluble Opadry, the coating solution concentration is 12-15%, the inlet air temperature of the coating pan is controlled at 60-70℃, and the tablet bed temperature is maintained at 38-42℃.

[0039] The technical solution of the present invention has been described above with reference to the preferred embodiments shown in the accompanying drawings. However, it will be readily understood by those skilled in the art that the scope of protection of the present invention is obviously not limited to these specific embodiments. Without departing from the principles of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will all fall within the scope of protection of the present invention.

[0040] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for producing a composition for reversing insulin resistance, characterized in that, include: Step S1, prepare the raw materials including: kudzu root extract, coptis extract, cinnamon extract, mulberry leaf extract, chromium pyridinecarboxylate and L-carnitine; Step S2: Crush and sieve the raw materials of each extract, and use high performance liquid chromatography to determine whether the content of key active ingredients in the raw materials meets the preset standards. The key active ingredients include puerarin, berberine, cinnamon polyphenols and DNJ. Step S3: If the content of the key active ingredient does not meet the preset standard, dynamically adjust the actual weight of each raw material within the weight ratio range of the key active ingredient. Step S4: Add the determined actual weights of kudzu root extract, coptis root extract, cinnamon extract, and mulberry leaf extract into a three-dimensional motion mixer and mix to obtain a uniform mixture of plant extracts. Step S5: Chromium pyridinecarboxylate and anhydrous ethanol are dispersed in a shear disperser to form a slurry, while L-carnitine and microcrystalline cellulose are diluted and premixed in equal increments to obtain a premix. Step S6: The plant extract mixture, slurry and premix are fed into a high-efficiency wet granulator, purified water is added as a binder and then granulated to obtain wet granules. Step S7: Determine the average particle size of the wet particles using a laser particle size analyzer, and determine the passability of the granulation process based on the average particle size. If the passability is not met, reduce the rate of adding the binder. Step S8: Under the condition that the granulation process is qualified, the wet granules are dried in a fluidized bed dryer and then oscillated and screened to obtain uniform dry granules. Step S9: After mixing the dry granules with magnesium stearate, the mixture is pressed into tablet cores using a high-speed tablet press, and then coated with a film coating premix in a high-efficiency coating pan.

2. The method for producing the composition for reversing insulin resistance according to claim 1, characterized in that, The ingredients are composed of the following parts by weight: 10-30 parts of kudzu root extract, 5-15 parts of coptis extract, 3-10 parts of cinnamon extract, 8-20 parts of mulberry leaf extract, 0.1-0.5 parts of chromium pyridinecarboxylate, and 2-8 parts of L-carnitine.

3. The method for producing the composition for reversing insulin resistance according to claim 2, characterized in that, The key active ingredient content standards in step S2 include: The content of puerarin in kudzu root extract is greater than or equal to the first preset content; The berberine content in Coptis chinensis extract is greater than or equal to the second preset content; The cinnamon polyphenol content in the cinnamon extract is greater than or equal to the third preset content; The DNJ content in mulberry leaf extract is greater than or equal to the fourth preset content.

4. The method for producing the composition for reversing insulin resistance according to claim 3, characterized in that, The kudzu root extract, coptis root extract, cinnamon extract, and mulberry leaf extract were all obtained by water extraction and alcohol precipitation or ultrasound-assisted extraction, and were then spray-dried into powder form.

5. The method for producing the composition for reversing insulin resistance according to claim 4, characterized in that, The weight ratio range of the key active ingredients in step S3 is as follows: 8-12 parts of puerarin, 2.5-4 parts of berberine, 0.6-1.2 parts of cinnamon polyphenols, and 0.16-0.24 parts of DNJ.

6. The method for producing the composition for reversing insulin resistance according to claim 5, characterized in that, In step S7, if the average particle size is greater than or equal to the preset particle size, the granulation process is deemed unqualified, and the addition rate of the adhesive is reduced based on the difference between the average particle size and the preset particle size.

7. The method for producing the composition for reversing insulin resistance according to claim 6, characterized in that, The drying process uses near-infrared spectroscopy technology to monitor the moisture content of the particles in real time online. When the moisture content reaches the preset level, the drying process automatically stops.

8. The method for producing the composition for reversing insulin resistance according to claim 7, characterized in that, The film coating premix is ​​gastrointestinal soluble Opadry, the coating solution concentration is 12-15%, the inlet air temperature of the coating pan is controlled at 60-70℃, and the tablet bed temperature is maintained at 38-42℃.

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