Diabetes embedded rod and preparation method thereof

Abstract

The invention relates to a diabetes mellitus implanting rod and a preparation method, and relates to the technical field of implanting rods, the diabetes mellitus implanting rod comprises a traditional Chinese medicine active component and a carrier material, the mass ratio of the traditional Chinese medicine active component to the carrier material is 1: 1, and according to the mass percentage of the diabetes mellitus implanting rod, the content of the traditional Chinese medicine active component is 1: 1. The carrier material comprises 3-7% of a drug carrying layer, 36-44% of a core layer and 3-7% of an outer layer; the traditional Chinese medicine active ingredients comprise 14-26% of astragalus polysaccharide, 13-17% of cortex phellodendri alkaloid, 8-12% of myrrh resin and 3-7% of polydatin, the medicine carrying layer is mesoporous silica nanoparticles, the core layer is a composite fiber of silk fibroin and polycaprolactone in a mass ratio of (1.5-2): 1, and the outer layer is a chitosan-sodium alginate coating. The traditional Chinese medicine active ingredients in the diabetes mellitus implant rod are substances such as polysaccharide extracted from Chinese herbal medicines, and the implant rod is made of natural macromolecular materials, so that the implant rod has good degradability and biocompatibility, rejection reaction and infection are avoided, and displacement or breakage can also be avoided.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of implant rods, in particular to a diabetes implant rod and a preparation method of the diabetes implant rod. BACKGROUND

[0002] China is the largest country of diabetes patients in the world. According to relevant data, one out of every ten people is a diabetes patient. The traditional treatment method for diabetes is single, almost all of which are lifelong oral hypoglycemic drugs, and only blood glucose can be controlled, not having the effect of "treatment and cure", and having the disadvantage of "relieving symptoms and aggravating the disease". Any drug has "side effects", and almost all hypoglycemic drugs have some damage to the liver and kidney function of the human body. With the lengthening of the medical history, the damage to the liver and kidney function is more severe and even failure, so the oral hypoglycemic drug therapy will make the patient fall into a "vicious cycle". Compared with oral drugs, insulin injection therapy has weaker gastrointestinal reactions and liver and kidney toxicity, but is more dependent; with the development of the disease, the amount of insulin also increases, and the principle of "use in and waste out" will make the body dependent on insulin.

[0003] Chinese patent application for invention with Chinese publication number CN113769012A discloses a preparation method for treating diabetes by odd acupoint catgut embedding, which is to soak catgut into traditional Chinese medicine liquid to obtain acupoint medicine thread, wherein the components of the traditional Chinese medicine liquid include yam, astragalus root, radix puerariae, radix trichosanthis, anemarrhena asphodeloides, schisandra chinensis, chicken gizzard, and medical alcohol. The obtained acupoint medicine thread is embedded into the acupoints of upper three huangs and lower three emperors. The rehabilitation treatment of diabetes patients by acupoint catgut embedding can reduce blood glucose, reduce the incidence of diseases with genetic tendency, and reduce the conversion rate of pre-diabetes population to diabetes, and can prevent and treat diabetic microangiopathy, diabetic gastrointestinal complications, and early diabetic nephropathy.

[0004] However, the immune function of diabetes patients is decreased due to high blood sugar environment, and the embedding wound is easy to become a channel for bacterial invasion. The catgut needs to pierce the skin to form a small wound, and if the aseptic operation is not strict (such as insufficient instrument disinfection or substandard operation environment), local infection or even systemic inflammation may be caused. Clinical reports show that although the incidence of infection is low, once it occurs, it may aggravate blood glucose fluctuation and form a vicious cycle. High blood sugar can inhibit the proliferation of fibroblasts and the synthesis of collagen, resulting in slow healing of the catgut embedding wound. Some patients may have line body rejection or local liquefactive necrosis, prolonging the recovery time. Research shows that the risk of postoperative delayed healing is significantly increased in patients with poor blood glucose control (HbA1c>7%). Traditional catgut may cause allergic reactions or local induration, and although the degradation of synthetic polymer thread body is controllable, the mechanical strength and flexibility are difficult to balance, which is easy to cause displacement or fracture. SUMMARY

[0005] In order to solve the above technical problems, the present application provides a diabetes implant rod and a preparation method.

[0006] In a first aspect, the present application provides a diabetes implant rod, which comprises a traditional Chinese medicine active ingredient and a carrier material, the mass ratio of the traditional Chinese medicine active ingredient and the carrier material is 1:1, the carrier material comprises 3-7% of a drug loading layer, 36-44% of a core layer and 3-7% of an outer layer according to the mass percentage of the diabetes implant rod; the traditional Chinese medicine active ingredient comprises 14-26% of Huang's polysaccharide, 13-17% of Huangbai alkaloids, 8-12% of Commiphora resin and 3-7% of polydatin, the drug loading layer is mesoporous silica nanoparticles, the core layer is a composite fiber of silk fibroin and polycaprolactone with a mass ratio of 1.5-2:1, and the outer layer is a chitosan-sodium alginate coating.

[0007] In the above technical solution, Huang's polysaccharide activates macrophages to polarize to M2 type through TLR4 receptors, up-regulates IL-10 secretion, reduces local TNF-α level of the wound, inhibits inflammation, stimulates fibroblast proliferation and accelerates collagen deposition, and promotes L cells in the intestinal tract to secrete GLP-1 and enhance insulin sensitivity.

[0008] Berberine in Huangbai alkaloids is embedded in bacterial DNA double strands to inhibit gyrase activity, is protonated in an acidic environment, greatly enhances membrane penetration, and at the same time blocks the NF-KB pathway to reduce the release of IL-6 and IL-1β.

[0009] The sesquiterpenes in Commiphora resin can inhibit the 5-LOX pathway, reduce the synthesis of prostaglandin PGE2, activate the VEGF signal at the same time, promote the migration of endothelial cells, and specifically inhibit the activity of MMP-9 to protect the extracellular matrix.

[0010] Polydatin up-regulates the expression of HO-1 and SOD2 through the Nrf2 pathway to scavenge ROS in a high blood sugar environment, and can also inhibit the TGF-β1 and Smad3 pathways to reduce scar formation and make the arrangement of collagen more regular.

[0011] Mesoporous silica has a high specific surface area, which can improve the drug loading rate, and can also protect the drug from enzymatic hydrolysis to prolong the action time.

[0012] Silk fibroin can provide excellent biocompatibility, cell adhesion promotion and controllable degradation. After blending with polycaprolactone, silk fibroin can provide certain mechanical strength. The fiber orientation arrangement of the whole core layer guides the ordered migration of cells, and improves the healing speed. And the softness conforms to the dynamic deformation of the tissue, reducing friction damage.

[0013] When the pH of chitosan is less than or equal to 6.5, -NH2 is protonated to -NH3 + , the coating swells and breaks. Sodium alginate competitively binds Ca 2+ in a high-sugar environment, and the ionic crosslinking network disintegrates. The whole outer layer can simultaneously perceive the pH drop and high-sugar environment during the infection process, and the precision exceeds that of single-response coatings. Chitosan itself inhibits bacterial membrane permeability, increases the antibacterial rate, and provides double protection.

[0014] Alternatively, the mesoporous silica nanoparticles are amino-modified mesoporous silica nanoparticles.

[0015] In the above technical solution, the amino-modified mesoporous silica can improve the drug loading rate and prolong the sustained-release time.

[0016] In a second aspect, the present application provides a preparation method of a diabetes implant rod, which comprises the following steps: Raw material processing: extraction and standardization of active ingredients of traditional Chinese medicine; Drug-loaded composite preparation: dissolve the phellodendron alkaloids and myrrh resin in ethanol, mix with mesoporous silica nanoparticles at a mass ratio of 1:4-6 to obtain a mixed solution, load for 25-35 min under the assistance of ultrasonic at 30-50 kHz, and dry at 55-65 DEG C under reduced pressure. Dissolve the astragalus polysaccharide and polyphenols in a PBS buffer solution with a pH of 7-7.5, mix with the mixture, stand still at 3-5 DEG C for 10-14 h, and collect the drug-loaded composite by centrifugation; Fiber spinning of the core layer: dissolve the silk fibroin solution and polycaprolactone in hexafluoroisopropanol, add the drug-loaded composite (15% of the total solid), magnetically stir for 22-26 h to form a homogeneous solution, and perform electrospinning under the conditions of an electric voltage of 16-20 kV, a receiving distance of 14-16 cm, a flow rate of 1-1.4 ml / h, a humidity of <40%, and a receiving roller rotating speed of 1800-2200 rpm to obtain oriented arrangement fibers, and then anneal the fibers in ethanol vapor for 22-26 h to obtain the core layer fibers; Coating of chitosan-sodium alginate: chitosan was dissolved in 1% acetic acid solution, sodium alginate was dissolved in deionized water, mixed according to the volume ratio of chitosan: sodium alginate 7:3 to obtain chitosan-sodium alginate mixed solution, the core fiber was immersed in the chitosan-sodium alginate mixed solution for 10-15s, the pulling speed was 1-3mm / s, immediately immersed in 3-8% CaCl2 solution for crosslinking for 25-35s, vacuum drying at 35-45℃ for 10-14h, then ethylene oxide sterilization treatment at 45-55℃, 50-70% humidity for 48-50h, to obtain a diabetes implant rod.

[0017] In the above technical solution, high-purity active ingredients are separated by solvent polarity and physical and chemical methods to avoid interference of impurities with subsequent drug loading and release.

[0018] The pore structure of mesoporous silica nanoparticles can limit the free diffusion of drugs and achieve long-term sustained release. The liposoluble components of phellodendri chinensis amorphous and myrrh resin are embedded in the channels of mesoporous silica nanoparticles, improving the drug loading rate. Astragalus polysaccharide is a negatively charged polysaccharide (-COO - group), and the surface of mesoporous silica nanoparticles is silicon hydroxyl (-SiOH), which is negatively charged in a neutral or alkaline environment, resulting in electrostatic repulsion. Some of the hydroxyl groups of astragalus polysaccharide form hydrogen bonds with the -SiOH on the surface of mesoporous silica nanoparticles, and some of the astragalus polysaccharide is mechanically retained in the pores of mesoporous silica nanoparticles. The hydrogen bonds of the silicon hydroxyl groups on the surface of mesoporous silica nanoparticles can form bonds with the phenolic hydroxyl groups of polygala root glycosides. This gradient drug loading design can allow hydrophobic drugs to be embedded in the pores and hydrophilic drugs to be adsorbed on the surface.

[0019] Polycaprolactone provides elastic modulus, and the beta-sheet structure of silk fibroin can enhance the tensile strength. The drug-loaded composite is dispersed in the interior of the fiber, which can avoid the cytotoxicity caused by local drug enrichment. The parallel arrangement of the fibers promotes the migration of fibroblasts along the tension direction.

[0020] pH and glucose response, chitosan is not protonated in normal tissues, sodium alginate is crosslinked with Ca 2+ Stable. Once infected or in high glucose conditions, the decrease in pH causes chitosan-NH2 to be converted to -NH3 + , glucose competitively binds Ca 2+ , causing the coating to swell and break, rapidly releasing the drug.

[0021] Alternatively, the preparation method further comprises dispersing the mesoporous silica nanoparticles in anhydrous toluene with a solid-liquid ratio of 1:50 under 40kHz ultrasonic for 30min to form a uniform suspension, then adding 3-aminopropyltriethoxysilane, refluxing in an oil bath at 110℃ for 6h, the solid-liquid ratio of the suspension to 3-aminopropyltriethoxysilane is 10:1, and centrifugal drying to obtain aminated mesoporous silica nanoparticles.

[0022] In the above technical solution, after the mesoporous silica nanoparticles are aminated, the -NH3 + Through electrostatic adsorption of the -COO - and the phenolic hydroxyl group of polydatin, the drug loading rate is improved, and the sustained release time is prolonged to more than 72 h.

[0023] In a third aspect, a diabetes implant rod or a preparation method of a diabetes implant rod prepared by the preparation method of the diabetes implant rod is applied in diabetes treatment.

[0024] In summary, the present application includes at least one of the following beneficial technical effects: 1. The astragalus polysaccharide in the active ingredient of traditional Chinese medicine in the present application can bidirectionally regulate immunity (anti-inflammatory + promote repair), avoid the immunosuppressive side effects of traditional antibiotics, the alkaloid of cortex phellodendri has high drug-resistant bacteria, the pH response releases the precise target infection site, the commiphora resin has both anti-inflammatory and healing functions, protects the extracellular matrix, and the polydatin can reduce scar formation and make the arrangement of collagen more regular.

[0025] 2. The mesoporous silica of the drug loading layer in the present application has a high specific surface area, can improve the drug loading rate, can also protect the drug from enzymatic hydrolysis, and prolongs the action time.

[0026] 3. The fiber orientation arrangement of the core layer in the present application guides the ordered migration of cells, improves the healing speed, and is flexible and conforms to the dynamic deformation of the tissue, reducing friction damage.

[0027] 4. The outer layer of the present application can simultaneously sense the pH decrease and high-sugar environment in the infection process, and the precision exceeds that of a single response coating. Chitosan itself inhibits bacterial membrane permeability, improves the antibacterial rate, and provides double protection. DETAILED DESCRIPTION

[0028] The present application will be further described in detail below in combination with examples.

[0029] The materials used in the following examples can be obtained by market purchase.

[0030] Example 1: The present embodiment provides a diabetes implant rod and a preparation method thereof.

[0031] The diabetes implant rod comprises a traditional Chinese medicine active ingredient and a carrier material, the mass ratio of the traditional Chinese medicine active ingredient and the carrier material is 1:1, the carrier material comprises 3% of a drug-loaded layer, 44% of a core layer and 3% of an outer layer according to the mass percentage of the diabetes implant rod; the traditional Chinese medicine active ingredient comprises 26% of Huangshi polysaccharide, 13% of Huangbai alkaloid, 8% of Mody resin and 3% of Huzhang glycoside, the drug-loaded layer is mesoporous silica nanoparticles, the core layer is a composite fiber of silk fibroin and polycaprolactone with a mass ratio of 1.5:1, and the outer layer is a chitosan-sodium alginate coating.

[0032] The preparation method comprises the following steps: S1, raw material treatment: S11, Huangqi polysaccharide extraction adopts water extraction and alcohol precipitation method: Huangqi dried roots are extracted in hot water at 80℃ for 3 times, and after filtration, the filtrate is concentrated, 4 times volume of 95% ethanol is added for precipitation, and the mixture is placed at 4℃ for 12h, and the polysaccharide precipitate is obtained by centrifugation; S12, Huangbai alkaloid extraction adopts acid water percolation method: 0.5% sulfuric acid solution is added to the dried bark of Huangbai at a flow rate of 1ml / min·kg, and the percolate is collected, and the percolate is passed through a cation exchange resin column, and total alkaloids are obtained by elution with ammonia water at pH 8-9; S13, Mody resin extraction adopts supercritical CO2 extraction: Somali Mody resin is extracted under the conditions of pressure 25MPa, temperature 45℃, entraining agent 5% ethanol, CO2 flow rate 25kg / h for 2.5h, and the sesquiterpene component is collected, and the content of mody acid is detected by HPLC to be ≥60%, and the total sesquiterpene is ≥25%; S14, extraction of Huzhang glycoside: dry rhizomes of Huzhang are selected, and 70% ethanol is added at a material-liquid ratio of 1:10, and the mixture is refluxed at 85℃ for 1.5h, and then filtered while hot, and then purified by AB-8 type macroporous resin, and then eluted with 30% ethanol, and then dried to obtain Huzhang glycoside.

[0033] S2, preparation of mesoporous silica nanoparticle drug-loaded composite: Huangbai alkaloid and Mody resin are dissolved in ethanol, mixed with mesoporous silica nanoparticles at a mass ratio of 1:5 to obtain a mixed solution, and then subjected to ultrasonic-assisted loading at 40kHz for 30min, and then dried at 60℃ under reduced pressure, and then Huangqi polysaccharide and Huzhang glycoside are dissolved in PBS buffer solution with pH 7.3, mixed with the mixture, placed at 4℃ for 12h, and then the drug-loaded composite is collected by centrifugation.

[0034] S3, fiber spinning of the core layer: S31, the preparation of silk fibroin solution comprises the following steps: degumming of domestic silkworm silk in 0.5% Na2CO3 solution for 30min, dissolving in 9.3M LiBr solution, dialysis purification, and then concentrated to 20% w / v to obtain silk fibroin solution; S32, Preparation of core layer fiber: dissolve the silk fibroin solution and polycaprolactone in hexafluoroisopropanol, add the drug-loaded complex (15% of the total solid), and magnetically stir for 24 h to form a homogeneous solution. Electrospinning is performed under the following conditions: voltage 18 kV, receiving distance 15 cm, flow rate 1.2 ml / h, humidity <40%, and receiving roller rotating speed 2000 rpm. Oriented fibers are obtained, and then ethanol vapor annealing is performed for 24 h to obtain the core layer fiber; S4, Coating of chitosan-sodium alginate coating: dissolve chitosan in 1% acetic acid solution, and dissolve sodium alginate in deionized water. A chitosan-sodium alginate mixed solution is obtained by mixing chitosan and sodium alginate at a volume ratio of 7:3. The core layer fiber is immersed in the chitosan-sodium alginate mixed solution for 13 s at a pulling speed of 2 mm / s, and then immediately immersed in a 5% CaCl2 solution for crosslinking for 30 s. Vacuum drying is performed at 40°C for 12 h, and then ethylene oxide sterilization treatment is performed at 50°C and 60% humidity for 48 h to obtain the diabetes implant rod.

[0035] Embodiment 2: The embodiment provides a diabetes implant rod and a preparation method thereof.

[0036] The diabetes implant rod comprises traditional Chinese medicine active ingredients and carrier materials, and the mass ratio of the traditional Chinese medicine active ingredients to the carrier materials is 1:1. According to the mass percentage of the diabetes implant rod, the carrier materials comprise 7% of a drug-loaded layer, 36% of a core layer, and 7% of an outer layer. The traditional Chinese medicine active ingredients comprise 14% of Huangshi polysaccharide, 17% of Huangbai alkaloids, 12% of Modyu resin, and 7% of Huozhang glycoside. The drug-loaded layer is mesoporous silica nanoparticles. The core layer is a composite fiber of silk fibroin and polycaprolactone at a mass ratio of 2:1. The outer layer is a chitosan-sodium alginate coating.

[0037] The preparation method of the diabetes implant rod is the same as that in Embodiment 1.

[0038] Embodiment 3: The embodiment provides a diabetes implant rod and a preparation method thereof.

[0039] The diabetes implant rod comprises traditional Chinese medicine active ingredients and carrier materials, and the mass ratio of the traditional Chinese medicine active ingredients to the carrier materials is 1:1. According to the mass percentage of the diabetes implant rod, the carrier materials comprise 7% of a drug-loaded layer, 36% of a core layer, and 7% of an outer layer. The traditional Chinese medicine active ingredients comprise 14% of Huangshi polysaccharide, 17% of Huangbai alkaloids, 12% of Modyu resin, and 7% of Huozhang glycoside. The drug-loaded layer is mesoporous silica nanoparticles. The core layer is a composite fiber of silk fibroin and polycaprolactone at a mass ratio of 2:1. The outer layer is a chitosan-sodium alginate coating.

[0040] The preparation method of the diabetes implant rod is the same as that in Embodiment 1.

[0041] Embodiment 4: The embodiment provides a diabetes implant rod and a preparation method thereof.

[0042] The diabetes implant rod comprises traditional Chinese medicine active ingredients and a carrier material, a mass ratio of the traditional Chinese medicine active ingredients and the carrier material is 1:1, the carrier material comprises 5% of a drug-loaded layer, 40% of a core layer and 5% of an outer layer according to mass percentage of the diabetes implant rod; the traditional Chinese medicine active ingredients comprise 20% of Huangshi polysaccharide, 15% of Huangbai alkaloids, 10% of Commiphora resin and 5% of polydatin, the drug-loaded layer is amino-modified mesoporous silica nanoparticles, the core layer is a composite fiber of silk fibroin and polycaprolactone with a mass ratio of 1.7:1, and the outer layer is a chitosan-sodium alginate coating.

[0043] The preparation method comprises the following steps: S1, raw material processing: S11, Huangqi polysaccharide extraction adopts water extraction and alcohol precipitation: Huangqi dried roots are extracted three times in hot water at 80 DEG C, and after filtration, the filtrate is concentrated, 4 times volume of 95% ethanol is added for precipitation, and the mixture is placed at 4 DEG C for 12 hours, and the polysaccharide precipitate is obtained by centrifugation; S12, Huangbai alkaloid extraction adopts acid water percolation: 0.5% sulfuric acid solution is added to the dried bark of Huangbai at a flow rate of 1 ml / min·kg, and the percolate is collected, and the percolate is passed through a cation exchange resin column, and total alkaloids are obtained by elution with ammonia water at pH 8-9; S13, Commiphora resin extraction adopts supercritical CO2 extraction: Somali Commiphora resin is extracted under the conditions of pressure 25 MPa, temperature 45 DEG C, entraining agent 5% ethanol, and CO2 flow rate 25 kg / h for 2.5 hours, and the sesquiterpene component is collected, and the content of Commiphora acid is detected by HPLC to be greater than or equal to 60% (UV 210 nm), and the total sesquiterpenes are greater than or equal to 25%; S14, polydatin extraction: dry rhizomes of Polygonum cuspidatum are selected, and 70% ethanol is added at a material-liquid ratio of 1:10, and the mixture is refluxed at 85 DEG C for 1.5 hours, and then filtered while hot, and AB-8 type macroporous resin is used for purification, and then 30% ethanol is added for elution, and polydatin is obtained by drying.

[0044] S2, preparation of drug-loaded composite: S21, preparation of amino-modified mesoporous silica nanoparticles: mesoporous silica nanoparticles are dispersed in anhydrous toluene at a solid-liquid ratio of 1:50 under ultrasonic treatment at 40 kHz for 30 minutes to form a uniform suspension, and then 3-aminopropyltriethoxysilane is added, and the mixture is refluxed in an oil bath at 110 DEG C for 6 hours, and the solid-liquid ratio of the suspension to 3-aminopropyltriethoxysilane is 10:1, and the amino-modified mesoporous silica nanoparticles are obtained by centrifugation and drying. S22, mesoporous silica nanoparticle drug-loaded composite preparation: dissolve the phellodendron alkaloids and myrrh resin in ethanol, mix with mesoporous silica nanoparticles at a mass ratio of 1:5 to obtain a mixed solution, load under the assistance of 40 kHz ultrasonic for 30 min, dry at 60°C under reduced pressure, dissolve the astragalus polysaccharide and polydatin in a PBS buffer solution with a pH of 7.3, mix with the mixture, stand still at 4°C for 12 h, and collect the drug-loaded composite by centrifugation.

[0045] S3, fiber spinning of the core layer: S31, the preparation of the silk fibroin solution is as follows: degum the domestic silkworm silk in a 0.5% Na2CO3 solution by boiling for 30 min, dissolve in a 9.3M LiBr solution, concentrate to 20% w / v after dialysis and purification, and obtain the silk fibroin solution; S32, preparation of the core layer fiber: dissolve the silk fibroin solution and polycaprolactone in hexafluoroisopropanol, add the drug-loaded composite (15% of the total solids), magnetically stir for 24 h to form a homogeneous solution, electrospun under the conditions of a voltage of 18 kV, a receiving distance of 15 cm, a flow rate of 1.2 ml / h, a humidity of <40%, and a receiving roller rotating speed of 2000 rpm, obtain the oriented arrangement fiber, and then steam anneal the fiber in ethanol for 24 h to obtain the core layer fiber; S4, coating of the chitosan-sodium alginate coating: dissolve chitosan in a 1% acetic acid solution, dissolve sodium alginate in deionized water, mix the chitosan and sodium alginate at a volume ratio of 7:3 to obtain a chitosan-sodium alginate mixture, immerse the core layer fiber in the chitosan-sodium alginate mixture for 13 s at a pulling speed of 2 mm / s, immediately immerse in a 5% CaCl2 solution for crosslinking for 30 s, dry at 40°C under vacuum for 12 h, and then perform ethylene oxide sterilization treatment at 50°C and a humidity of 60% for 48 h to obtain the diabetes implant rod.

[0046] The following are treatment cases of acupoint implantation using the implant rod prepared by the embodiment of the present application: Case 1: Patient, Zhang, female, 78 years old, developed polydipsia, polyphagia, polyuria, accompanied by weight loss, daily water intake increased significantly, food intake increased, nocturia increased, an average of 8 times / night, at that time, there was no dysuria, no urinary irritation symptoms, body weight decreased from 65 kg to 53 kg, now 49 kg, blood glucose was high, diagnosed as diabetes, insulin hypoglycemia, observed in our hospital, fasting blood glucose 11.55 mmol / L, total protein 54.4 mmol / L, albumin 30.2 mmol / L, BUN 15 mmol / L, Cr 255 umol / L, CHO 7.83 mmol / L, random blood glucose above 30 mmol / L, insulin hypoglycemia was used, and was admitted to hospital as "type 2 diabetes".

[0047] Physical examination: T: 36.5℃, P: 72 times / min, R: 20 times / min, Bp: 170 / 95 mmHg, clear consciousness, normal development. Normal skin color, no edema, rash, subcutaneous nodules, lumps, spider veins, and scars. Hair growth, normal distribution, shiny.

[0048] Treatment: subcutaneous implantation of Zhongwan point, fully expose the required acupoint for implantation, after routine disinfection, use 1% lidocaine for local anesthesia, implant the prepared implant rod of Example 1 into the subcutaneous tissue of Zhongwan point through special instruments. After implantation, apply adhesive tape and press locally for 15-20 minutes to prevent bleeding and infection. Remove the adhesive tape after 48 hours. 1 time is 1 course, 1 course is 3 years, and the second implantation will be performed after 3 years according to the patient's condition.

[0049] Efficacy: After fourteen months of treatment, the fasting blood glucose was controlled at 7.7 mmol / L-8.3 mmol / L, and the two-hour postprandial blood glucose was controlled at 10.6-11.8 mmol / L, without infection.

[0050] Case Two: Patient, Zhang, female, 60 years old, with polydipsia, polyphagia, polyuria, weight loss, nocturia, average 7 times / night, body weight decreased from 69 kg to 54 kg, now 50 kg, blood glucose is high, diagnosed as diabetes, fasting blood glucose 11.3 mmol / L, total protein 51.8 mmol / L, albumin 31.5 mmol / L, BUN 15 mmol / L, Cr 249 umol / L, CHO 7.84 mmol / L, random blood glucose above 27 mmol / L, insulin was used to reduce blood sugar, and was admitted to hospital as "type 2 diabetes".

[0051] Physical examination: T: 36.2℃, P: 88 times / min, R: 20 times / min, Bp: 140 / 85 mmHg, clear consciousness, normal development, moderate nutrition, automatic position, and cooperative examination. No edema, rash, petechiae, purpura. Hair growth, normal distribution, shiny. Supraclavicular, axillary, trochlea, inguinal, axillary lymph nodes were not enlarged.

[0052] Treatment: subcutaneous implantation of Zhongwan point, fully expose the required acupoint for implantation, after routine disinfection, use 1% lidocaine for local anesthesia, implant the prepared implant rod of Example 2 into the subcutaneous tissue of Zhongwan point through special instruments. After implantation, apply adhesive tape and press locally for 15-20 minutes to prevent bleeding and infection. Remove the adhesive tape after 48 hours. 1 time is 1 course, 1 course is 3 years, and the second implantation will be performed after 3 years according to the patient's condition.

[0053] Efficacy: After 15 months of treatment, the fasting blood glucose control was 7.3mmol / L~8.2mmol / L, and the two-hour postprandial blood glucose control was 9.8~12.9mmol / L, with no infection.

[0054] Case three: Patient, Li, male, 45 years old, ten years ago, without obvious inducement, polydipsia, polyphagia, polyuria, with weight loss, daily water consumption increased significantly, food volume increased, nocturia frequency, an average of 6 times / night or so, at that time, no dysuria, no urinary irritation symptoms, body weight decreased from 80 kg to 60 kg, now 55 kg, blood glucose is high, diagnosed as diabetes, once taking Xiaoke pill treatment, without monitoring blood glucose, control is unknown, three days ago in our hospital, fasting blood glucose 11.82mmol / L, total protein 53.9mmol / L, albumin 29.8mmol / L, BUN 14mmol / L, Cr 257umol / L, CHO 7.78mmol / L, random blood glucose above 31mmol / L, insulin was used to reduce blood sugar, and was admitted to hospital as "type 2 diabetes".

[0055] Physical examination: T: 36.8℃, P: 82 times / min, R: 17 times / min, BP: 165 / 95 mmHg, conscious, normal development. The skin color of the whole body is normal, without edema, rash, subcutaneous nodule, mass, spider nevi, and scar. Hair growth, distribution is normal, with luster.

[0056] Treatment: subcutaneous implantation of Zhongwan point, fully expose the implanted acupoint, after routine disinfection, use 1% lidocaine for local anesthesia, implant the implant rod prepared in Example 3 into the subcutaneous tissue of Zhongwan point through special instruments. After implantation, stick a band-aid and press locally for 15-20 minutes to prevent bleeding and infection. Remove the band-aid after 48 hours. 1 time is 1 course of treatment, 1 course of treatment is 3 years, and the second implantation is performed after 3 years according to the patient's condition.

[0057] Efficacy: After 12 months of treatment, the fasting blood glucose control was 7.5mmol / L~8.31mmol / L, and the two-hour postprandial blood glucose control was 10.2~11.1mmol / L, with no infection.

[0058] Case four: Patient, Wang, female, 55 years old, seven years ago, polydipsia, polyphagia, polyuria, weight loss, frequent nocturia, an average of 7 times per night, body weight gradually decreased from 62 kg to 52 kg, now 48 kg, blood glucose is high, diagnosis of diabetes, fasting blood glucose 12.3 mmol / L, total protein 52.8 mmol / L, albumin 31.5 mmol / L, BUN 15 mmol / L, Cr 251 umol / L, CHO 7.91 mmol / L, random blood glucose above 28 mmol / L, use insulin to reduce sugar, with "type 2 diabetes" admitted to hospital.

[0059] Physical examination: T: 36.8℃, P: 80 times / min, R: 17 times / min, BP: 160 / 90 mmHg, clear consciousness, normal development, moderate nutrition, automatic position, cooperative examination. No edema, rash, petechiae, purpura. Hair growth, normal distribution, luster. Supraclavicular, axillary, trochlea, inguinal, axillary lymph nodes were not enlarged.

[0060] Treatment: subcutaneous implantation of Zhongwan point, fully expose the implanted acupoint, after routine disinfection, use 1% lidocaine for local anesthesia, implant the implant rod prepared in Example 4 into the subcutaneous tissue of Zhongwan point through special instruments. After implantation, apply adhesive tape and press the local area for 15-20 minutes to prevent bleeding and infection. Remove the adhesive tape after 48 hours. 1 time is 1 course, 1 course is 3 years, and the second implantation is performed after 3 years according to the patient's condition.

[0061] Efficacy: After nine months of treatment, the fasting blood glucose was controlled at 7.0 mmol / L-8.2 mmol / L, and the two-hour postprandial blood glucose was controlled at 9.5-12.5 mmol / L, without infection.

[0062] Case five: Patient, Cheng, male, 65 years old, eight years ago, polydipsia, polyphagia, polyuria, weight loss, frequent nocturia, an average of 7 times per night, body weight gradually decreased from 72 kg to 62 kg, now 48 kg, blood glucose is high, diagnosis of diabetes, fasting blood glucose 12.3 mmol / L, total protein 52.2 mmol / L, albumin 33 mmol / L, BUN 16 mmol / L, Cr 249 umol / L, CHO 7.88 mmol / L, random blood glucose above 28 mmol / L, use insulin to reduce sugar, with "type 2 diabetes" admitted to hospital.

[0063] Physical examination: T: 36.8℃, P: 84 times / min, R: 18 times / min, BP: 160 / 90 mmHg, clear consciousness, normal development, moderate nutrition, automatic position, cooperative examination. No edema, rash, petechiae, purpura. Hair growth, normal distribution, luster. Supraclavicular, axillary, trochlea, inguinal, axillary lymph nodes were not enlarged.

[0064] Treatment: subcutaneous implantation of Zhongwan acupoint, fully expose the acupoint required for implantation, after routine disinfection, local anesthesia with 1% lidocaine, implant the prepared implant rod of Example 4 into the subcutaneous of Zhongwan acupoint through special instruments. After implantation, stick a band-aid and press locally for 15-20 minutes to prevent bleeding and infection, and remove the band-aid after 48 hours. Once is a course of treatment, one course is 3 years, and the second implantation is performed after 3 years according to the patient's condition.

[0065] Efficacy: After eight months of treatment, the fasting blood glucose was controlled at 6.8mmol / L~8.7mmol / L, and the two-hour postprandial blood glucose was controlled at 9.6~13.5mmol / L, without infection.

[0066] Case six: Patient, Li, male, 62 years old, with polydipsia, polyphagia, polyuria, weight loss, nocturia, average 7 times / night, body weight gradually decreased from 80 kg to 68 kg, now 63 kg, blood glucose is high, diagnosed as diabetes, fasting blood glucose 12.8mmol / L, total protein 55.0mmol / L, albumin 31.2mmol / L, BUN 16mmol / L, Cr 255umol / L, CHO 7.91mmol / L, random blood glucose above 30mmol / L, insulin is used to reduce blood sugar, and is admitted to hospital as "type 2 diabetes".

[0067] Physical examination: T: 36.8℃, P: 76 times / minute, R: 19 times / minute, BP: 162 / 92 mmHg, clear consciousness, normal development, moderate nutrition, automatic body position, physical examination cooperation. No edema, rash, ecchymosis, purpura. Normal hair growth and distribution, with luster. No enlargement of supraclavicular, axillary, trochlear, inguinal, axillary lymph nodes.

[0068] Treatment: subcutaneous implantation of Zhongwan acupoint, fully expose the acupoint required for implantation, after routine disinfection, local anesthesia with 1% lidocaine, implant the prepared implant rod of Example 4 into the subcutaneous of Zhongwan acupoint through special instruments. After implantation, stick a band-aid and press locally for 15-20 minutes to prevent bleeding and infection, and remove the band-aid after 48 hours. Once is a course of treatment, one course is 3 years, and the second implantation is performed after 3 years according to the patient's condition.

[0069] Efficacy: After six months of treatment, the fasting blood glucose was controlled at 6.5mmol / L~7.4mmol / L, and the two-hour postprandial blood glucose was controlled at 8.7~11.6mmol / L, without infection.

[0070] The above are preferred embodiments of the present application, but do not limit the protection scope of the present application, therefore: any equivalent changes made in structure, shape, principle according to the present application should be covered within the protection scope of the present application.

Claims

1. A diabetes implant stick, characterized in that, The diabetes implant stick comprises traditional Chinese medicine active ingredients and carrier material, with a mass ratio of 1:

1. Based on the mass percentage of the diabetes implant stick, the carrier material comprises 3-7% drug-loaded layer, 36-44% core layer, and 3-7% outer layer. The traditional Chinese medicine active ingredients comprise 14-26% *Phellodendron amurense* polysaccharide, 13-17% *Phellodendron chinense* alkaloids, 8-12% myrrh resin, and 3-7% *Polygonum cuspidatum* glycoside. The drug-loaded layer is mesoporous silica nanoparticles. The core layer is a composite fiber of silk fibroin and polycaprolactone with a mass ratio of 1.5-2:

1. The outer layer is a chitosan-sodium alginate coating.

2. The diabetes implant stick according to claim 1, characterized in that, The mesoporous silica nanoparticles are mesoporous silica nanoparticles modified by amylation.

3. A method for preparing a diabetes implant stick as described in any one of claims 1-2, characterized in that, The preparation method includes the following steps: Raw material processing: Extraction and standardization of active ingredients from traditional Chinese medicine; Preparation of drug-loaded complex: Phellodendron chinense alkaloids and myrrh resin were dissolved in ethanol and mixed with mesoporous silica nanoparticles at a mass ratio of 1:4-6 to obtain a mixture. The mixture was subjected to ultrasonic loading at 30-50 kHz for 25-35 min and dried under reduced pressure at 55-65 °C. Astragalus polysaccharide and polydipsia glycoside were dissolved in PBS buffer at pH 7-7.5 and mixed with the mixture. The mixture was allowed to stand at 3-5 °C for 10-14 h and then collected by centrifugation. Core layer fiber spinning: Silk fibroin solution and polycaprolactone are dissolved in hexafluoroisopropanol, and drug-loaded complex (accounting for 15% of total solids) is added. The solution is magnetically stirred for 22-26 hours to form a homogeneous solution. Electrospinning is carried out under the conditions of voltage 16-20kV, receiving distance 14-16cm, flow rate 1-1.4ml / h, humidity <40%, and receiving roller rotation speed 1800-2200rpm to obtain oriented fibers. Then, the core layer fibers are obtained by annealing with ethanol vapor for 22-26 hours. Chitosan-sodium alginate coating: Chitosan is dissolved in 1% acetic acid solution, and sodium alginate is dissolved in deionized water. The chitosan and sodium alginate are mixed at a volume ratio of 7:3 to obtain a chitosan-sodium alginate mixture. The core fiber is immersed in the chitosan-sodium alginate mixture for 10-15 seconds at a pulling speed of 1-3 mm / s, and then immediately immersed in 3-8% CaCl2 solution for crosslinking for 25-35 seconds. It is then vacuum dried at 35-45℃ for 10-14 hours, and then sterilized with ethylene oxide at 45-55℃ and 50-70% humidity for 48-50 hours to obtain a diabetic implant rod.

4. A method for preparing a diabetic implant stick according to claim 3, characterized in that, The preparation method further includes dispersing mesoporous silica nanoparticles in anhydrous toluene with a solid-liquid ratio of 1:50 and sonicating at 40 kHz for 30 min to form a uniform suspension, then adding 3-aminopropyltriethoxysilane and refluxing in an oil bath at 110 °C for 6 h. The solid-liquid ratio of the suspension to 3-aminopropyltriethoxysilane is 10:

1. After centrifugation and drying, aminated mesoporous silica nanoparticles are obtained.

5. The application of a diabetes implant stick in the treatment of diabetes, characterized in that, The diabetes implant stick is prepared using the method described in any one of claims 1-2, or the method described in any one of claims 3-4.