Chitosan cervical membrane powder and preparation method thereof

Abstract

The invention discloses chitosan cervical membrane powder and a preparation method thereof. The raw materials comprise quantitative water-soluble chitosan, gelatin, a complex chitosan iodine solution, glycerol, Tween 80, a sodium polyacrylate solution, phosphoric acid or acetic acid and water. The preparation method comprises the following steps: dissolving the water-soluble chitosan, the gelatin, the complex chitosan iodine solution, the glycerol, the Tween 80, the sodium polyacrylate solution and the phosphoric acid or the acetic acid in water, uniformly stirring until the gel is formed, injecting the gel into a mold, freezing and drying in vacuum to obtain a membrane with the weight of 120-200mg and the thickness of 1-2mm, and crushing and sieving to obtain medicine powder. Porous spongy antibacterial powder is prepared from carboxymethyl chitosan, gelatin and complex chitosan iodine, so that the water absorption performance and the controlled release of iodine are enhanced; compared with ball-shaped microsphere powder, the powder with the semi-continuous lamellar structure further promotes contact between the medicine and the biological environment, efficient transmission and controllable release are achieved, and the medicine effect can last for 3-7 days.

Description

Technical Field

[0001] The invention relates to the technical field, and in particular to a chitosan cervical membrane powder and a preparation method thereof. Background Art

[0002] Cervicitis, vaginitis, and cervical ulcer are common diseases among women, and their incidence rates are relatively high. Patients with the disease have unbearable itching, excessive leucorrhea, and foul smell. They are also susceptible to infection, recurrence, and erosion and bleeding, which bring great pain to patients. In particular, patients with chronic cervicitis, if not treated in time, are prone to cervical cancer. Currently, there are two commonly used treatment methods for cervicitis and vaginitis, one is to irrigate with liquid medicine, and the other is to insert tablets, suppositories, capsules, etc. into the lesion position of the vagina. However, tablets, suppositories, and capsules are difficult to reach and stay in the lesion position, and their efficacy is also difficult to maintain for a long time, thereby greatly affecting the efficacy of the drug.

[0003] Patent document CN116942642A discloses a shell-iodine cervical antibacterial membrane, which is made of chitosan, shell iodine and other materials. It includes a circular main body and a circular convex column at the center of its upper surface. When in use, the circular convex column can be inserted into the cervical canal, and the circular main body is applied on the surface of the cervix. It can be used for repairing and anti-inflammatory wounds after cervical surgery (LEEP, laser, electrocoagulation, freezing, etc.), and has antibacterial, anti-inflammatory, hemostatic, detumescent, and prevents epithelial eversion of the cervical canal. However, the placement process of the above antibacterial membrane is complicated, and it is still difficult for patients or family members to operate it at home after simple training. In actual use, it still needs to be operated by professionals, which not only increases the medical burden of patients, but also limits its promotion in daily clinical applications. Summary of the invention

[0004] In order to facilitate self-care for patients and reduce the medical burden, the present invention provides a chitosan cervical membrane powder and a preparation method thereof.

[0005] The technical scheme adopted by the present invention is as follows: a chitosan cervical membrane powder, the microstructure of which is a fragmented powder; the raw materials are formulated according to the weight ratio: 6%-10% of water-soluble chitosan, 5-10% of gelatin, 20-35% of complex shell iodine solution, 0.4-1% of glycerol, 0.5-2% of Tween 80, 10%-15% of 1-2wt% sodium polyacrylate solution, 0.2-0.8% of phosphoric acid or acetic acid, and the balance is water.

[0006] Preferably, the maximum length and width of the fragmented medicinal powder is less than 50 μm, and the thickness is 1-3 μm.

[0007] The second set of technical schemes adopted by the present invention is as follows: a method for preparing chitosan cervical membrane powder, comprising dissolving quantitatively proportioned water-soluble chitosan, gelatin, complexed shell iodine solution, glycerol, Tween 80, sodium polyacrylate solution and phosphoric acid or acetic acid in water, stirring evenly until the mixture is in a gel state, injecting the mixture into a mold and freeze-drying the mixture in a vacuum to obtain a membrane sheet with a weight of 120-200 mg and a thickness of 1-2 mm, and crushing and sieving the membrane sheet to obtain a fine and uniform powder.

[0008] Preferably, the steps are as follows: Step 1, adjusting the pH of distilled water with acetic acid or phosphoric acid; Step 2, adding gelatin to the solution and stirring to dissolve; Step 3, adding water-soluble chitosan to the solution in small amounts and multiple times, stirring to dissolve; Step 4: add glycerol, Tween 80 and complex shell iodine solution to the solution in sequence, stir evenly, then add sodium polyacrylate solution, and continue stirring to form a smooth and delicate gel; Step 5, injecting the gel into the mold, pre-freezing the mold, then demoulding, and then refreezing the membrane; Step six, performing sublimation drying to obtain a dry film; Step seven, crushing to obtain uniform medicine powder.

[0009] Preferably, the specific steps are as follows: Step 1, weigh water for injection and add it into a stainless steel pot, control the water bath temperature at 45-60°C, add phosphoric acid and stir, and adjust the pH value to 2.0-3.0; Step 2, weigh gelatin and add the solution, place it in a vacuum stirring container, control the water bath temperature at 45-60°C, and continue stirring until the gelatin is completely dissolved; Step 3, add carboxymethyl chitosan in small amounts and multiple times in a vacuum stirring container, control the water bath temperature at 30-45°C, and continue stirring to dissolve until the carboxymethyl chitosan is completely dissolved and becomes a gel; Step 4: Add glycerol and Tween 80 in a vacuum stirring container in sequence, control the water bath temperature at 25-30°C, add the complex shell iodine solution and stir evenly, then add the sodium polyacrylate solution and continue stirring until a smooth and delicate gel is formed; Step 5: Use a glue injection machine to inject the gel into the mold, place the mold in an ultra-low temperature refrigerator at -45°C to -35°C for pre-freezing, then demould, and then place the membrane in an ultra-low temperature refrigerator at -50°C to -45°C for secondary freezing; Step 6, using a vacuum freeze dryer to perform sublimation drying to obtain a dry film; Step seven, using a high-energy ball mill and a jet mill to crush, and obtaining a uniform powder after sieving through a 100-200 mesh sieve.

[0010] Preferably, the preparation steps of the complex shell iodine solution are as follows: Step 4.1, preparation of grafted material: Take a certain amount of carboxymethyl chitosan to prepare a 1-2wt% carboxymethyl chitosan solution; add 0.1-1wt% ammonium persulfate as an initiator under nitrogen protection, and react for 0.5-1h; add N-vinyl pyrrolidone with a mass of 2-8 times that of the carboxymethyl chitosan, heat to 60-70°C, and react for 2-8h; wash the reaction product with ethanol for 4-5 times, and vacuum dry to obtain a grafted powder; Step 4.2, complexation with iodine: Take a certain amount of graft powder to prepare a graft solution of 1-7wt%, and adjust the pH value to between 5 and 6 with acetic acid; take 7-15 times the weight of the graft substance and 6-12 times the weight of the graft substance, and add water and tert-butyl alcohol to fully dissolve; mix the graft solution with the iodine solution and the potassium iodide solution, and carry out complex reaction for 6-10 hours to obtain a complex shell iodine solution.

[0011] The third set of technical solutions adopted by the present invention is as follows: a chitosan cervical membrane powder delivery device, comprising a slender cylinder, a piston, a push rod and a cap; the piston is assembled in the cylinder, the front end forms a space for storing the chitosan cervical membrane powder, and the rear end is installed as a whole with the push rod; the cap is installed at the front end opening of the cylinder.

[0012] The present invention has the following beneficial effects: 1. The drug powder has the characteristics of water absorption and film formation. It forms a natural film after combining with tissue fluid or skin secretions. The drug can quickly reach and evenly disperse in the lesion to achieve the purpose of killing viruses and bacteria; 2. Compared with spherical microsphere powder, semi-continuous flaky structure powder can promote the contact between drugs and the biological environment, and the formed membrane and receptors have better interaction, which helps to achieve more efficient drug delivery. In addition, the larger volume surface area ratio is conducive to more controlled drug release, which helps to form a sustained-release dosage form and prolong the shelf life of the drug; 3. Carboxymethyl chitosan, gelatin and complex shell iodine are used as the base material, supplemented with glycerol, Tween 80 and sodium polyacrylate solution, and then the antibacterial powder is prepared by freeze vacuum drying process, so that the powder has a porous sponge-like organizational structure, which enhances the water absorption performance of the powder and can enhance the controlled release of iodine, so that it is slowly released, and the efficacy can last for 3 to 7 days; 4. In the preparation process of the complex shell iodine solution, selecting materials and chemical reaction conditions with strong reaction efficiency and good biocompatibility can effectively improve the stability and availability of the complex shell iodine solution. Through the complexation reaction of iodine chloride, higher hydrophilicity and biocompatibility can be achieved. At the same time, the dissociation reaction is promoted and the release of effective iodine is improved, which can ensure that the final product has a stronger effect in drug treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 This is an electron microscope image (350 times) of the existing antibacterial powder.

[0014] Figure 2 This is an electron microscope image (350 times) of the antibacterial powder according to an embodiment of the present invention.

[0015] Figure 3 This is an electron microscope image (5000 times) of the existing antibacterial powder.

[0016] Figure 4 This is an electron microscope image (5000 times) of the antibacterial powder according to an embodiment of the present invention.

[0017] Figure 5 This is an electron microscope image (10,000 times) of the existing antibacterial powder.

[0018] Figure 6 This is an electron microscope image (10,000 times) of the antibacterial powder according to an embodiment of the present invention.

[0019] Figure 7 This is an electron microscope image of the existing antibacterial powder (15,000 times).

[0020] Figure 8 This is an electron microscope image (15,000 times) of the antibacterial powder according to an embodiment of the present invention.

[0021] Fig. 9 2 is a cross-sectional view of a medicine delivery device according to an embodiment of the present invention.

[0022] Fig.10 Schematic diagram of the medicine delivery device in the embodiment of the present invention completing medicine delivery.

[0023] In the figure, there are a cylinder 1, a piston 2, a push rod 3, a cap 4, and medicine powder 5. DETAILED DESCRIPTION

[0024] The present invention will be further described below in conjunction with the embodiments and drawings.

[0025] Embodiment, a chitosan cervical membrane powder, the raw materials are formulated according to the weight ratio: 6%-10% water-soluble chitosan, 5-10% gelatin, 20-35% complex shell iodine solution, 0.4-1% glycerol, 0.5-2% Tween 80, 10%-15% 1~2wt% sodium polyacrylate solution, 0.2-0.8% phosphoric acid or acetic acid, and the balance is water. Its preparation method is: dissolve the quantitatively proportioned water-soluble chitosan, gelatin, complex shell iodine solution, glycerol, Tween 80, sodium polyacrylate solution and phosphoric acid or acetic acid in water, stir evenly until it is gel-like, inject into a mold and freeze-dry in a vacuum to obtain a membrane with a weight of 120~200mg and a thickness of 1~2mm, and obtain the powder after crushing and sieving.

[0026] The specific steps of the above preparation method of this embodiment are as follows.

[0027] Step 1: Weigh water for injection and add it into a stainless steel pot. Control the water bath temperature at 45-60°C. Add phosphoric acid and stir to adjust the pH value to 2.0-3.0.

[0028] Step 2: Weigh gelatin and add it to the solution, place it in a vacuum stirring container, control the water bath temperature at 45-60°C, and continue stirring until the gelatin is completely dissolved.

[0029] Step 3: Add carboxymethyl chitosan in small amounts and multiple times in a vacuum stirring container, control the water bath temperature at 30-45° C., and continue stirring to dissolve until the carboxymethyl chitosan is completely dissolved and becomes gel-like.

[0030] Step 4: Add glycerol and Tween 80 in a vacuum stirring container in sequence, control the water bath temperature at 25-30° C., add the complex shell iodine solution and stir evenly, then add the sodium polyacrylate solution and continue stirring until a smooth and delicate gel is formed.

[0031] Wherein, the process steps of complex shell iodine solution are as follows: Step 4.1, preparing the graft: taking a certain amount of carboxymethyl chitosan to prepare a 1-2wt% carboxymethyl chitosan solution; adding 0.1-1wt% ammonium persulfate as an initiator under nitrogen protection, and reacting for 0.5-1h; adding N-vinyl pyrrolidone with a mass of 2-8 times that of the carboxymethyl chitosan, heating to 60-70°C, and reacting for 2-8h; washing the reaction product with ethanol for 4-5 times, and vacuum drying to obtain a graft powder; Step 4.2, complexation with iodine: take a certain amount of graft powder to prepare a 1-7wt% graft solution, and adjust the pH value to between 5 and 6 with acetic acid; take 7-15 times the weight of the grafted substance and 6-12 times the weight of the grafted substance. Potassium iodide, add water and tert-butanol to fully dissolve; mix the graft solution with the iodine solution and the potassium iodide solution, and carry out complexation reaction for 6-10 hours to obtain a complex shell iodine solution.

[0032] Step 5: Use a glue injection machine to inject the gel into the mold, place the mold in an ultra-low temperature refrigerator at -45°C to -35°C for pre-freezing, then demould, and then place the membrane in an ultra-low temperature refrigerator at -50°C to -45°C for secondary freezing; Step 6, using a vacuum freeze dryer to perform sublimation drying to obtain a dry film; Step seven, using a high-energy ball mill and a jet mill to crush, and obtaining a uniform powder after sieving through a 100-200 mesh sieve.

[0033] The antibacterial powder prepared by the above steps is a fine and uniform powder in the form of microscopic fragments.

[0034] Figure 1 , Figure 2 The electron microscope images of the existing antibacterial powder and the antibacterial powder of this embodiment observed under an electron microscope with a magnification of 350 times are shown. Among them, the existing antibacterial powder is in the form of dispersed particles, while the product of this embodiment is in the form of crumbs.

[0035] Figure 3 , Figure 4 The electron microscope images of the existing antibacterial powder and the antibacterial powder of this embodiment observed under an electron microscope with a magnification of 5000 times. Among them, the existing antibacterial powder is in the form of a ball, the diameter of the ball is between 2-12 microns, and the surface of the microsphere is adhered to smaller particles, making the surface rough; the product of this embodiment is a semi-continuous thin sheet structure, the maximum length and width of the sheet structure within the field of view is not more than 32.40μm, and the thickness is not more than 2.30μm.

[0036] Figure 5 , Figure 6 The electron microscope images of the existing antibacterial powder and the antibacterial powder of this embodiment observed under an electron microscope with a magnification of 10,000 times are shown. Among them, the existing antibacterial powder has an irregular spherical structure, with small particles attached to the surface, and the boundaries between the spherical structures are clear and the intervals are relatively far; the product of this embodiment has a continuous sheet structure with a relatively smooth and flat surface.

[0037] Figure 7 , Figure 8 The electron microscope images of the existing antibacterial powder and the antibacterial powder of this embodiment observed under an electron microscope with a magnification of 15,000 times are shown. Among them, the spherical particles of the existing antibacterial powder are of different sizes, and irregular small particle structures are attached to the surface, and the sample is darker in the field of vision; the product of this embodiment is brighter in the field of vision, and there are fine protrusions on the surface of the thin sheet, which is relatively flat as a whole, reflecting that the particle size of the sample is relatively uniform.

[0038] In the embodiment, Fig. 9As shown, a chitosan cervical membrane powder delivery device includes an elongated barrel 1, a piston 2, a push rod 3 and a cap 4; the piston 2 is assembled in the barrel 1, the front end forms a space for storing the chitosan cervical membrane powder as claimed in claim 1, and the rear end is installed as a whole with the push rod 3; the cap 4 is installed at the front end opening of the barrel 1. The antibacterial powder is filled into the front end of the barrel 1, the push rod 3 is pushed into place, and then the cap 4 is covered. During the drug delivery operation, Fig.10 As shown, when the rear end of the push rod 3 is pushed to be flush with the cylinder 1, the front end surface of the piston 2 also just extends out of the cylinder 1, thereby ensuring full utilization of the medicine powder 5.

[0039] Obviously, the above embodiments of the present invention are only examples for explaining the present invention, and are not intended to limit the implementation methods of the present invention. Other obvious changes or modifications derived from the essence of the present invention still fall within the protection scope of the present invention.

Claims

1. A chitosan cervical membrane powder, characterized in that: The microstructure is fragmented powder; the raw materials are formulated according to weight ratio: 6%-10% water-soluble chitosan, 5-10% gelatin, 20-35% complex shell iodine solution, 0.4-1% glycerol, 0.5-2% Tween 80, 10%-15% 1~2wt% sodium polyacrylate solution, 0.2-0.8% phosphoric acid or acetic acid, and the balance is water.

2. The chitosan cervical membrane powder according to claim 1, characterized in that: The maximum length and width of the fragmented medicinal powder is less than 50 μm, and the thickness is 1-3 μm.

3. A method for preparing chitosan cervical membrane powder, characterized in that: Dissolve quantitatively proportioned water-soluble chitosan, gelatin, complex shell iodine solution, glycerol, Tween 80, sodium polyacrylate solution and phosphoric acid or acetic acid in water, stir evenly until it becomes a gel state, inject into a mold and freeze-dry in a vacuum to obtain a film with a weight of 120-200 mg and a thickness of 1-2 mm, which is then crushed and sieved to obtain a fine and uniform powder.

4. The method for preparing the chitosan cervical membrane powder according to claim 3, characterized in that: Here are the steps: Step 1, adjusting the pH of distilled water with acetic acid or phosphoric acid; Step 2, adding gelatin to the solution and stirring to dissolve; Step 3, adding water-soluble chitosan to the solution in small amounts and multiple times, stirring to dissolve; Step 4: add glycerol, Tween 80 and complex shell iodine solution to the solution in sequence, stir evenly, then add sodium polyacrylate solution, and continue stirring to form a smooth and delicate gel; Step 5, injecting the gel into the mold, pre-freezing the mold, then demoulding, and then refreezing the membrane; Step six, performing sublimation drying to obtain a dry film; Step seven, crushing to obtain uniform medicine powder.

5. The method for preparing the chitosan cervical membrane powder according to claim 4, characterized in that: The specific steps are as follows: Step 1, weigh water for injection and add it into a stainless steel pot, control the water bath temperature at 45-60°C, add phosphoric acid and stir, and adjust the pH value to 2.0-3.0; Step 2, weigh gelatin and add the solution, place it in a vacuum stirring container, control the water bath temperature at 45-60°C, and continue stirring until the gelatin is completely dissolved; Step 3, add carboxymethyl chitosan in small amounts and multiple times in a vacuum stirring container, control the water bath temperature at 30-45°C, and continue stirring to dissolve until the carboxymethyl chitosan is completely dissolved and becomes a gel; Step 4: Add glycerol and Tween 80 in a vacuum stirring container in sequence, control the water bath temperature at 25-30°C, add the complex shell iodine solution and stir evenly, then add the sodium polyacrylate solution and continue stirring until a smooth and delicate gel is formed; Step 5: Use a glue injection machine to inject the gel into the mold, place the mold in an ultra-low temperature refrigerator at -45°C to -35°C for pre-freezing, then demould, and then place the membrane in an ultra-low temperature refrigerator at -50°C to -45°C for secondary freezing; Step 6, using a vacuum freeze dryer to perform sublimation drying to obtain a dry film; Step seven, using a high-energy ball mill and a jet mill to crush, and obtaining a uniform powder after sieving through a 100-200 mesh sieve.

6. The method for preparing the chitosan cervical membrane powder according to any one of claims 3 to 5, characterized in that: The preparation steps of the complex shell iodine solution are as follows: Step 4.1, preparation of grafted material: Take a certain amount of carboxymethyl chitosan to prepare a 1-2wt% carboxymethyl chitosan solution; Add 0.1-1wt% ammonium persulfate as initiator under nitrogen protection and react for 0.5-1h; Add 2-8 times the mass of carboxymethyl chitosan N-vinyl pyrrolidone, raise the temperature to 60-70°C, and react for 2-8 hours; The reaction product was washed with ethanol for 4-5 times and vacuum dried to obtain grafted powder; Step 4.2, complexation with iodine: A certain amount of graft powder is taken to prepare a 1-7 wt % graft solution, and the pH value is adjusted to between 5 and 6 with acetic acid; Take 7-15 times the weight of the grafted substance of elemental iodine and 6-12 times the weight of the grafted substance of potassium iodide, add water and tert-butyl alcohol to fully dissolve; The graft solution is mixed with iodine solution and potassium iodide solution, and the complexation reaction is carried out for 6-10 hours to obtain a complex shell iodine solution.

7. A medicine delivery device for chitosan cervical membrane powder, characterized in that: It comprises an elongated cylinder (1), a piston (2), a push rod (3) and a cap (4); the piston (2) is assembled in the cylinder (1), the front end of which forms a space for storing the chitosan cervical membrane powder as claimed in claim 1, and the rear end is integrally mounted with the push rod (3); the cap (4) is mounted at the front end opening of the cylinder (1).

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