Novel biguanide chitosan instrument with compound glycyrrhizin serving as medicine loaded by encapsulated nanoparticles

Abstract

The invention discloses a novel biguanide chitosan instrument with compound glycyrrhizin serving as a drug loaded by encapsulated nanoparticles, and mainly relates to the field of medical instruments. Comprising compound glycyrrhizin liquid which is accurately extracted from Chinese herbal medicines by combining a high performance liquid chromatography technology with a specific purification process and is prepared according to a scientific proportion, and the magnetic targeting Fe3O4-coated HA nano particle carrier is used for carrying the compound glycyrrhizin liquid to realize accurate targeting delivery of the medicine under the action of an external magnetic field. The invention has the beneficial effects that the targeting property and the bioavailability of the medicine are obviously improved, the precise delivery of the medicine is realized, and the medicine waste and the adverse reaction are reduced. Through the application of a magnetic targeting technology and a nanoparticle carrier, the medicine can reach a focus part more accurately, and the treatment effect is improved. Due to the small-size effect of the nanoparticle carrier and the surface modification technology, the stability and biocompatibility of the drug in vivo are improved, the distribution and metabolism of the drug in a non-targeted part are reduced, and the occurrence risk of side effects of the drug is reduced.

Description

Technical Field

[0001] The present invention relates to the field of medical devices, and specifically to a novel biguanide chitosan device encapsulating nanoparticles loaded with compound glycyrrhizin Background Art

[0002] The statements in this part only provide background technical information related to the present invention and do not necessarily constitute prior art

[0003] Psoriasis is a chronic relapsing inflammatory skin disease with a long course and extremely easy to relapse. It not only affects the image of patients, but also brings severe itching and pain to patients, greatly reducing the quality of life of patients. At present, there are a variety of drugs for the treatment of psoriasis, but there are generally many problems. Some drugs have poor efficacy and are difficult to effectively control the progression of the disease, resulting in patients needing to take medicine for a long time, increasing the treatment cost and the pain of patients. Moreover, many drugs have relatively serious adverse reactions, which not only affect the treatment compliance of patients, but may also cause further damage to the physical health of patients

[0004] In the field of medical devices, although there are also some devices for the treatment of psoriasis, such as ultraviolet light therapy devices, etc., most of these devices can only play an auxiliary treatment role and cannot fundamentally solve the problems existing in drugs. Moreover, some devices are complex to operate and require professional personnel to operate, restricting their popularization and application in primary medical institutions and patients' families

[0005] In view of the various deficiencies of existing treatment drugs and devices, it is of great practical significance to develop a novel, highly efficient and low - side - effect treatment device. The novel biguanide chitosan device encapsulating nanoparticles loaded with compound glycyrrhizin involved in the present invention is developed based on this background. The device realizes the precise delivery and highly efficient treatment of drugs by loading compound glycyrrhizin solution on the magnetic - targeting Fe3O3@HA nanoparticle carrier and then encapsulating it in the micro - needles of biguanide chitosan material Summary of the Invention

[0006] The object of the present invention is to provide a novel biguanide chitosan device encapsulating nanoparticles loaded with compound glycyrrhizin, which significantly improves the targeting and bioavailability of the drug, realizes the precise delivery of the drug, reduces drug waste and adverse reactions. Through the application of magnetic targeting technology and nanoparticle carriers, the drug can reach the lesion site more accurately, improving the treatment effect. Specifically, under the action of an external magnetic field, the magnetic targeting Fe3O3@HA nanoparticle carrier can precisely direct to the psoriasis lesion area, significantly increasing the concentration of compound glycyrrhizin solution at the lesion site, thereby enhancing the efficacy of the drug. At the same time, the small size effect and surface modification technology of the nanoparticle carrier further improve the stability and biocompatibility of the drug in vivo, reduce the distribution and metabolism of the drug in non-target sites, and lower the risk of drug side effects.

[0007] To achieve the above object, the present invention is realized through the following technical solutions:

[0008] A novel biguanide chitosan device encapsulating nanoparticles loaded with compound glycyrrhizin includes;

[0009] Compound glycyrrhizin solution, which is precisely extracted from Chinese herbal medicines through high-performance liquid chromatography technology combined with specific purification processes and scientifically proportioned; magnetic targeting Fe3O4@HA nanoparticle carrier, used to carry the compound glycyrrhizin solution to achieve precise targeted delivery of the drug under the action of an external magnetic field, and this carrier has excellent magnetic responsiveness and biocompatibility; biguanide chitosan material microneedles, used to encapsulate the magnetic targeting Fe3O4@HA nanoparticle carrier carrying the compound glycyrrhizin solution, and the biguanide chitosan material microneedles have a small volume and precise shape, can penetrate the skin surface layer directly to the lesion site, and the biguanide chitosan material microneedles have the property of clearing extracellular free DNA, which can inhibit the development of psoriasis from the source.

[0010] The preparation of the compound glycyrrhizin solution involves screening, extracting, and purifying steps of Chinese herbal medicine raw materials to remove impurities, retain active ingredients, and make each component reach the best ratio through advanced proportioning technology. The magnetic targeting Fe3O4@HA nanoparticle carrier is prepared by chemical synthesis methods, and nanoparticles with uniform particle size and good dispersibility are obtained by precisely controlling the reaction conditions, and the nanoparticles are surface-modified to enhance their biocompatibility and magnetic responsiveness.

[0011] The biguanide chitosan material microneedles are prepared by micro-nano processing technology, precisely controlling the size and shape of the microneedles so that they can easily penetrate the skin surface layer, and the microneedles are subjected to drug loading and encapsulation treatments to ensure that the compound glycyrrhizin solution exists stably in the microneedles and is slowly released after penetrating the skin.

[0012] The loading method of the magnetic targeting Fe3O4@HA nanoparticle carrier and the compound glycyrrhizin solution is to ensure the stable loading of the compound glycyrrhizin solution on the nanoparticle carrier through specific chemical bonding / or physical adsorption methods. After encapsulating and loading the magnetic targeting Fe3O4@HA nanoparticle carrier carrying the compound glycyrrhizin solution, the metformin chitosan material microneedles are encapsulated to ensure that the drug does not leak during storage and transportation.

[0013] It also includes a drug release monitoring system for real-time monitoring of the release of the compound glycyrrhizin solution in the microneedles and feedback of the monitoring data to an external control device to adjust the magnetic field parameters and drug release rate according to the patient's condition. It also includes an intelligent control system for automatically adjusting the magnetic field parameters and drug release rate according to the patient's condition and treatment progress to achieve intelligent treatment.

[0014] A novel metformin chitosan device encapsulating a nanoparticle drug loaded with compound glycyrrhizin includes:

[0015] 1. Compound glycyrrhizin solution: In this invention, high-performance liquid chromatography technology is utilized, combined with advanced purification processes, to precisely extract natural drug components from Chinese herbal medicines and develop a compound glycyrrhizin solution with a specific ratio through scientific formulation. This process ensures the purity and activity of the drug components, making it have a significant anti-inflammatory effect and providing strong drug support for the treatment of psoriasis.

[0016] 2. Magnetic targeting Fe3O3@HA nanoparticle carrier: In this invention, magnetic targeting Fe3O3@HA nanoparticles are selected as the loading carrier for the compound glycyrrhizin solution. These nanoparticles have excellent magnetic responsiveness and biocompatibility, can be precisely guided to the lesion site under the action of an external magnetic field to achieve precise drug delivery. At the same time, the nanoparticle carrier can also improve the targeting and bioavailability of the drug, reduce the non-specific distribution of the drug in the body, and thus reduce drug side effects.

[0017] 3. Metformin chitosan material microneedles: In this invention, the magnetic targeting nanoparticles carrying the compound glycyrrhizin solution are encapsulated in the metformin chitosan material microneedles. These microneedles have a small volume and precise morphology and can easily penetrate the skin surface to reach the lesion site. As a natural cationic polymer, metformin chitosan not only has good biocompatibility and degradability but also has the property of clearing extracellular free DNA (cfDNA). This property can inhibit the development of psoriasis from the source and reduce the patient's inflammatory response and skin damage.

[0018] During the preparation process, the present invention adopts advanced microneedle preparation technology to ensure that the size, shape and drug loading of the microneedles reach the optimal state. At the same time, by optimizing the preparation process of the nanoparticle carrier, the stability and targeting of the drug are improved. The application of these technical means has significantly improved the therapeutic effect and safety of the novel metformin chitosan device encapsulating nanoparticles loaded with compound glycyrrhizin of the present invention.

[0019] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0020] Significantly improve the targeting and bioavailability of the drug, achieve precise drug delivery, reduce drug waste and adverse reactions. Through the application of magnetic targeting technology and nanoparticle carriers, the drug can reach the lesion site more accurately, improving the therapeutic effect. Specifically, under the action of an external magnetic field, the magnetic targeting Fe3O3@HA nanoparticle carrier can accurately guide to the psoriasis lesion area, significantly increasing the concentration of compound glycyrrhizin solution at the lesion site, thereby enhancing the efficacy of the drug. At the same time, the small size effect and surface modification technology of the nanoparticle carrier further improve the stability and biocompatibility of the drug in vivo, reduce the distribution and metabolism of the drug in non-target sites, and reduce the risk of drug side effects.

[0021] Use metformin chitosan to remove cfDNA and inhibit the development of psoriasis from the source, improving the therapeutic effect. Metformin chitosan, as a natural cationic polymer, has a unique ability to remove extracellular free DNA (cfDNA). During the pathogenesis of psoriasis, the abnormal accumulation of cfDNA will activate the immune system, trigger inflammatory reactions and skin damage. Metformin chitosan can bind to cfDNA through electrostatic interaction to form a stable complex, thereby effectively removing cfDNA in the body.

[0022] Adopt natural herbal medicine ingredients with small side effects and low dependence as therapeutic drugs to reduce the risk of adverse reactions and liver and kidney damage during the treatment process. The compound glycyrrhizin solution selected in the present invention is a natural medicine ingredient extracted from Chinese herbal medicines and prepared through scientific proportioning and advanced purification processes. Compared with traditional chemically synthesized drugs, natural herbal medicine ingredients have the advantages of small side effects and low dependence. During the treatment of psoriasis, patients often need to take medicine for a long time to control the condition, and traditional drugs may cause damage to the liver and kidney functions of patients. The natural herbal medicine ingredients adopted in the present invention can effectively reduce this risk and ensure the treatment safety of patients. At the same time, the multiple active ingredients in the compound glycyrrhizin solution can also act synergistically to enhance the efficacy of the drug and improve the treatment compliance of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Appendix Figure 1It is a preparation flow chart of a novel biguanide chitosan device encapsulating nanoparticles loaded with compound glycyrrhizin according to the present invention. Specific embodiments

[0024] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by this application.

[0025] The present invention relates to a novel biguanide chitosan device encapsulating nanoparticles loaded with compound glycyrrhizin, and its main structure includes

[0026] Preparation of compound glycyrrhizin solution

[0027] Raw material screening; select Chinese herbal medicine raw materials, such as licorice. Preliminary tests are carried out on the raw materials using professional detection methods, including appearance inspection, moisture content determination, effective ingredient content detection, etc. The moisture content is determined by the loss on drying method to ensure that the moisture content of the licorice raw material meets the standard and avoid deterioration of the raw material due to excessive moisture. The effective ingredient content is detected using advanced technologies such as high performance liquid chromatography (HPLC) to accurately determine the content of components such as glycyrrhizic acid and liquiritin in licorice.

[0028] Extraction and purification; extraction is carried out using high performance liquid chromatography technology. This technology uses advanced chromatographic columns and mobile phase systems to efficiently separate various components in Chinese herbal medicine. During the extraction process, parameters such as temperature, pressure, and flow rate are precisely controlled to ensure the maximum extraction of effective ingredients. After the licorice raw material is crushed, an appropriate amount of extraction solvent is added, and extraction is carried out at a specific temperature (such as 60 - 80 °C) and normal pressure conditions at a certain flow rate (such as 1 - 2 ml / min). The extracted solution needs to undergo multiple purification operations to remove impurities and retain the effective ingredients. During the extraction process, a suitable extractant is selected, and separation is carried out according to the solubility differences of different components in different solvents. During crystallization, by controlling conditions such as temperature and concentration, the effective ingredients are precipitated in crystal form. Strict quality control is carried out for each purification operation, and means such as thin layer chromatography (TLC) and infrared spectroscopy (IR) are used to detect the purification effect to ensure that the purified compound glycyrrhizin solution has high purity and stable quality.

[0029] Scientific proportioning; according to the treatment requirements of psoriasis and the pharmacological effects of each component in the compound glycyrrhizin solution, advanced proportioning technology is used, and through precise calculation and experimental verification, each component reaches the optimal ratio. The proportioned compound glycyrrhizin solution needs to undergo stability tests, including accelerated tests such as high temperature, high humidity, and light, as well as long-term stability tests, to ensure that there are no component changes or failures during storage and use.

[0030] Preparation of magnetic targeting Fe3O4@HA nanoparticle carriers; Chemical synthesis:

[0031] Magnetic targeting Fe3O4@HA nanoparticles are prepared by advanced chemical synthesis methods such as solvothermal method or co-precipitation method. In the solvothermal method, raw materials such as iron salts and hyaluronic acid (HA) are mixed in a certain proportion, an appropriate amount of solvent is added, and the reaction is carried out in a high-temperature and high-pressure reaction kettle. By adjusting conditions such as reaction temperature (e.g., 180 - 220 °C), time (e.g., 12 - 24 hours), pH value (e.g., 8 - 10), etc., nanoparticles with uniform particle size and good dispersibility are obtained. During the reaction process, techniques such as dynamic light scattering (DLS) are used to monitor the particle size and dispersibility of the nanoparticles in real time.

[0032] Surface modification; The synthesized nanoparticles are surface-modified to enhance their biocompatibility and magnetic responsiveness. Specific chemical reagents are used to modify the nanoparticles, such as connecting biocompatible molecules to the nanoparticle surface by chemical bonding or physical adsorption methods. Biocompatible molecules such as polyethylene glycol (PEG) are used to modify the nanoparticles to reduce the immune response of the nanoparticles in the body. The surface-modified nanoparticles need to be subjected to biocompatibility tests and magnetic responsiveness tests. The biocompatibility tests are carried out by methods such as cytotoxicity tests and animal experiments to ensure their safe application in the body. The magnetic responsiveness test observes the movement of the nanoparticles by applying an external magnetic field to ensure that they can effectively respond to the external magnetic field.

[0033] Preparation of metformin chitosan material microneedles; Micro-nano processing:

[0034] Metformin chitosan material microneedles are prepared by advanced micro-nano processing techniques such as photolithography, etching, and nanoimprinting. By precisely controlling the size and shape of the microneedles, they have a small volume and precise morphology and can easily penetrate the skin surface to reach the lesion site. The electron beam lithography technique is used to precisely control parameters such as the diameter (e.g., 50 - 100 μm) and length (e.g., 500 - 1000 μm) of the microneedles. During the micro-nano processing, high-precision processing equipment and advanced process parameters are used.

[0035] Drug loading and encapsulation

[0036] The microneedles are subjected to drug loading and encapsulation processes, and the magnetic targeting Fe3O4@HA nanoparticle carriers carrying compound glycyrrhizin solution are stably loaded into the microneedles. Specific methods, such as soaking, spraying, etc., are used to ensure the stable existence and slow release of the drug in the microneedles. For example, the microneedles are soaked in a solution containing nanoparticle carriers, and by controlling the soaking time and solution concentration, the drug is uniformly loaded into the microneedles. At the same time, the microneedles are encapsulated, and polymer encapsulation technology is used to prevent drug leakage during storage and transportation. The encapsulated microneedles need to be tested for tightness to ensure no drug leakage.

[0037] Assembly and Encapsulation of the Device

[0038] Loading of Nanoparticles with Drugs: The compound glycyrrhizin solution is stably loaded onto the magnetic targeting Fe3O4@HA nanoparticle carriers through specific chemical bonding or physical adsorption methods. During the loading process, the drug loading amount is strictly controlled, and methods such as ultraviolet-visible spectrophotometry are used to accurately measure the drug loading amount to ensure that the drug can be evenly and stably distributed on the nanoparticle carriers.

[0039] Encapsulation of Microneedles: The nanoparticle carriers carrying drugs are encapsulated in the metformin chitosan material microneedles. Advanced encapsulation processes, such as vacuum encapsulation or nitrogen encapsulation processes, are used, and at the same time, the mechanical properties and skin penetration of the microneedles are strictly tested. Mechanical property tests include tensile tests, bending tests, etc., and a universal material testing machine is used for testing to ensure that the microneedles have sufficient mechanical strength. Skin penetration tests are carried out using ex vivo skin or animal skin, and by observing the depth and speed of the microneedles penetrating the skin, it is verified whether the microneedles can smoothly penetrate the skin and release the drug.

[0040] Use and Monitoring of the Device

[0041] External Magnetic Field-Assisted Targeted Drug Delivery: When using this device, in cooperation with an external magnetic field generating device, by adjusting the intensity and direction of the magnetic field, the aggregation and drug release of the magnetic targeting Fe3O4@HA nanoparticle carriers carrying compound glycyrrhizin solution at the lesion site are precisely controlled. The magnetic field generating device uses advanced electromagnetic technology and can precisely adjust the magnetic field parameters according to the size and depth of the lesion site.

[0042] Drug Release Monitoring and Adjustment: The device is equipped with a drug release monitoring system to monitor the release of the compound glycyrrhizin solution in the microneedles in real time. The monitoring data is fed back to the external control device through wireless transmission technology, and the doctor adjusts the magnetic field parameters and drug release rate according to the patient's condition and treatment progress. For example, when it is monitored that the drug release rate is too fast, the magnetic field intensity can be appropriately reduced to slow down the drug release.

[0043] Ensuring the Safety and Effectiveness of the Device

[0044] Safety assessment of nanoparticle carriers: During the preparation of magnetically targeted Fe3O4@HA nanoparticle carriers, strict toxicity tests and biocompatibility evaluations are carried out. The safety and effectiveness of nanoparticle carriers in vivo are evaluated by combining animal experiments and cell experiments.

[0045] Performance verification of microneedles: Mechanical property tests and skin penetration tests are carried out on microneedles made of biguanide chitosan materials. Mechanical property tests include tensile tests, bending tests, etc., which are carried out using a universal material testing machine to ensure that the microneedles have sufficient mechanical strength. Skin penetration tests are carried out using ex vivo skin or animal skin to verify whether the microneedles can smoothly penetrate the skin and release drugs.

[0046] Intelligentization and aseptic treatment of the device

[0047] Application of intelligent control system: The device is equipped with an intelligent control system, which adopts advanced algorithms and sensor technologies to automatically adjust the magnetic field parameters and drug release rate according to the patient's condition and treatment progress. For example, by analyzing indicators such as the patient's skin barrier function and degree of inflammation, the intelligent control system can accurately optimize the treatment plan.

[0048] Sterilization treatment: Strict sterilization treatment is carried out before the device is used, using methods such as autoclaving and radiation sterilization. During the sterilization process, sterilization parameters are strictly controlled, such as temperature (121°C, 15 minutes), radiation dose, etc., to ensure the aseptic state of the device. At the same time, the sterilization effect is verified, such as using biological indicators and other methods, to ensure an aseptic environment during the treatment process.

[0049] Detailed instructions for use:

[0050] Significantly improve the targeting and bioavailability of drugs, achieve precise drug delivery, reduce drug waste and adverse reactions. Through the application of magnetic targeting technology and nanoparticle carriers, drugs can reach the lesion site more accurately, improving the treatment effect. Specifically, under the action of an external magnetic field, the magnetically targeted Fe3O3@HA nanoparticle carrier can accurately guide to the psoriasis lesion area, making the concentration of compound glycyrrhizin solution at the lesion site increase significantly, thus enhancing the efficacy of the drug. At the same time, the small size effect and surface modification technology of the nanoparticle carrier further improve the stability and biocompatibility of the drug in vivo, reduce the distribution and metabolism of the drug in non-target sites, and reduce the risk of drug side effects.

[0051] Use natural herbal medicine ingredients with small side effects and low dependence as therapeutic drugs to reduce the risk of adverse reactions and liver and kidney damage during the treatment process. The compound glycyrrhizin solution selected in the present invention is a natural medicine ingredient extracted from Chinese herbal medicines and is prepared through scientific proportioning and advanced purification processes. Compared with traditional chemically synthesized drugs, natural herbal medicine ingredients have the advantages of small side effects and low dependence. During the treatment of psoriasis, patients often need to take medicine for a long time to control the condition, while traditional drugs may cause damage to the liver and kidney functions of patients. However, the natural herbal medicine ingredients adopted in the present invention can effectively reduce this risk and ensure the treatment safety of patients. At the same time, various active ingredients in the compound glycyrrhizin solution can also act synergistically to enhance the efficacy of the drug and improve the treatment compliance of patients.

Claims

1. A novel biguanide chitosan device encapsulating nanoparticles loaded with compound glycyrrhizin as a drug, characterized in that: Comprising; Compound glycyrrhizin solution, precisely extracted from Chinese herbal medicines by high-performance liquid chromatography technology combined with a specific purification process and scientifically proportioned; Magnetic targeting Fe3O4@HA nanoparticle carrier, used to carry the compound glycyrrhizin solution to achieve precise targeted delivery of the drug under the action of an external magnetic field. This carrier has excellent magnetic responsiveness and biocompatibility; Biguanide chitosan material microneedles, used to encapsulate the magnetic targeting Fe3O4@HA nanoparticle carrier carrying the compound glycyrrhizin solution. The biguanide chitosan material microneedles have a small volume and precise morphology, can penetrate the skin surface layer directly to the lesion site, and the biguanide chitosan material microneedles have the property of clearing extracellular free DNA, which can inhibit the development of psoriasis from the source.

2. The novel biguanide chitosan device with encapsulated nanoparticles loaded with compound glycyrrhizin as claimed in claim 1, wherein: The preparation of the compound glycyrrhizin solution removes impurities through operations such as screening of Chinese herbal medicine raw materials, extraction, and purification steps, retains the active ingredients, and makes each component reach the optimal ratio through advanced proportioning technology.

3. The novel biguanide chitosan device encapsulating nanoparticles loaded with compound glycyrrhizin as the drug according to claim 2, characterized in that: The magnetic targeting Fe3O4@HA nanoparticle carrier is prepared by a chemical synthesis method. Nanoparticles with uniform particle size and good dispersibility are obtained by precisely controlling the reaction conditions, and the nanoparticles are surface-modified to enhance their biocompatibility and magnetic responsiveness.

4. The novel biguanide chitosan device encapsulating nanoparticles loaded with compound glycyrrhizin as a drug according to claim 3, wherein: The biguanide chitosan material microneedles are prepared by micro-nano processing technology. The size and shape of the microneedles are precisely controlled to enable them to easily penetrate the skin surface layer, and the microneedles are subjected to drug loading and encapsulation treatments to ensure that the compound glycyrrhizin solution is stably present in the microneedles and slowly released after penetrating the skin.

5. The novel biguanide chitosan device encapsulating nanoparticles loaded with compound glycyrrhizin as a drug according to claim 4, characterized in that: The loading method of the magnetic targeting Fe3O4@HA nanoparticle carrier and the compound glycyrrhizin solution is through a specific chemical bonding / or physical adsorption method to ensure that the compound glycyrrhizin solution is stably loaded on the nanoparticle carrier.

6. The novel biguanide chitosan device with nano-particle drug encapsulation of compound glycyrrhizin according to claim 5, characterized in that: After the biguanide chitosan material microneedles encapsulate the magnetic targeting Fe3O4@HA nanoparticle carrier carrying the compound glycyrrhizin solution, they are encapsulated to ensure that the drug does not leak during storage and transportation.

7. The novel biguanide chitosan device with encapsulated nanoparticles loaded with compound glycyrrhizin as claimed in claim 6, wherein: It also includes a drug release monitoring system, used to monitor the release of the compound glycyrrhizin solution in the microneedles in real time and feedback the monitoring data to an external control device so as to adjust the magnetic field parameters and drug release rate according to the patient's condition.

8. The novel biguanide chitosan device with nano-particle encapsulated drug being compound glycyrrhizin according to claim 7, characterized in that: It also includes an intelligent control system, used to automatically adjust the magnetic field parameters and drug release rate according to the patient's condition and treatment progress to achieve intelligent treatment.

Images