A pharmaceutical composition for treating pseudomyopia, a preparation method thereof and an application thereof
By combining scopolamine and tropicamide and loading them onto halloysite nanotube complexes, a sustained-release eye drop solution was prepared, which solved the problems of poor efficacy and poor patient compliance of existing drugs. This solution achieved long-lasting, slow release, improving the treatment effect of pseudomyopia and patient compliance.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- BEIJING WEI VISION BUSINESS MANAGEMENT CO LTD
- Filing Date
- 2025-09-16
- Publication Date
- 2026-06-09
AI Technical Summary
Existing medications for treating pseudomyopia have problems such as poor efficacy, significant side effects, or poor patient compliance. Furthermore, existing eye drops have a short duration of action and require frequent administration.
An eye drop solution was prepared by using scopolamine and tropicamide in combination, and by loading a hyaluronic acid-tannic acid-cyclodextrin complex onto halloysite nanotubes to form a sustained-release gel layer. The mass ratio of scopolamine to tropicamide was 1:0.5-1:5. A pH adjuster, an osmotic pressure adjuster, and a preservative were added to achieve the sustained-release effect.
It achieves long-lasting, slow-release of active ingredients, increases the duration of efficacy, reduces side effects, enhances patient compliance, and provides a more stable treatment option for pseudomyopia.
Smart Images
Figure CN120939009B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical technology, specifically to a pharmaceutical composition for treating pseudomyopia, its preparation method, and its application. Background Technology
[0002] Myopia is a common eye disease, especially prevalent among teenagers. Pseudomyopia is caused by excessive eye strain, leading to sustained contraction and spasm of the ciliary muscle, increased lens thickness, and blurred vision. If left untreated, pseudomyopia can easily develop into true myopia, causing significant inconvenience to the patient's life and studies.
[0003] Currently, there are numerous methods and medications available for treating pseudomyopia on the market, but they all have various shortcomings. Some physical therapy methods have limited effectiveness and require long-term patient adherence, leading to poor compliance. Existing medications for pseudomyopia also suffer from problems such as poor efficacy, significant side effects, or unstable quality. Therefore, developing a medication for treating pseudomyopia that is effective, has few side effects, and is of stable quality has significant clinical importance and market demand.
[0004] Literature reports the treatment of pseudomyopia in adolescents with scopolamine hydrobromide eye drops (Huang Caifeng. Preparation and application of scopolamine hydrobromide eye drops [J]. Chinese Pharmaceutical Journal, 1980, 15(3): 12-15). This literature discloses the treatment of pseudomyopia with scopolamine hydrobromide eye drops. Scopolamine has cholinergic nerve blocking effect and can eliminate ciliary muscle spasm. In addition, it also has the effect of dilating capillaries and improving ocular microcirculation. Therefore, it can be used to treat pseudomyopia. Our hospital used eye drops prepared with this product to treat pseudomyopia in adolescents and achieved good results with an effective rate of 91.18%.
[0005] In addition, some literature reports the use of tropicamide in the treatment of pseudomyopia in children and adolescents and for cycloplegic refraction during ophthalmological examinations. Tropicamide's effects and toxicity are similar to atropine, but weaker. Its mydriatic effect is faster than atropine, but its duration of action is shorter, starting 5-20 minutes after instillation, reaching its maximum at 30-90 minutes, and lasting 18-48 minutes. Pupils generally return to normal within 12-36 hours. Furthermore, conventional eye drops have drawbacks such as short duration of action (e.g., tropicamide's effect is only 18-48 minutes), requiring frequent administration (multiple times daily), and poor patient compliance. Summary of the Invention
[0006] The purpose of this invention is to provide the use of scopolamine and tropicamide in combination in the preparation of a medicament for treating pseudomyopia. This invention also provides a pharmaceutical composition for treating pseudomyopia.
[0007] The technical solution of this invention is implemented as follows:
[0008] The present invention provides a pharmaceutical composition for treating pseudomyopia, comprising scopolamine or a pharmaceutically acceptable salt thereof, and tropicamide or a pharmaceutically acceptable salt thereof, wherein the mass ratio of scopolamine to tropicamide is 1:0.5-1:5.
[0009] As a further improvement of the present invention, in the pharmaceutical composition, the concentration of scopolamine is 0.01-0.1 w / v and the concentration of tropicamide is 0.05-0.5 w / v.
[0010] As a further improvement of the present invention, it also includes a pH adjuster, an osmotic pressure adjuster, a preservative, and a solvent.
[0011] As a further improvement of the present invention, the pH adjuster is a boric acid-borax buffer system, which adjusts the pH value to 5.0-7.0.
[0012] As a further improvement of the present invention, the osmotic pressure regulator is potassium chloride or sodium chloride; the preservative is benzalkonium chloride; and the solvent is water for injection.
[0013] The present invention further protects a method for preparing the above-mentioned pharmaceutical composition for treating pseudomyopia, comprising the following steps:
[0014] S1. Halloysite nanotubes were added to water, along with hyaluronic acid, tannic acid, and cyclodextrin, and a catalyst was added. The mixture was subjected to hydrothermal reaction, centrifuged, washed, and dried to obtain modified halloysite nanotubes.
[0015] S2. Scopolamine and tropicamide were dissolved in water, modified halloysite nanotubes were added, the mixture was stirred and mixed evenly, centrifuged, washed and dried to obtain loaded nanotubes;
[0016] S3. Add the loaded nanotubes to water for injection, add a buffer to adjust the pH to 5.0-7.0, add an osmotic pressure regulator and a preservative, add water for injection to the full volume, sterilize, and dispense to obtain a pharmaceutical composition for treating pseudomyopia.
[0017] As a further improvement of the present invention, the mass ratio of halloysite nanotubes, hyaluronic acid, tannic acid, cyclodextrin and catalyst in step S1 is 10-15:4-6:2-3:3-5:0.2-0.5, the catalyst is a Tris-HCl solution with a pH of 8-9, the hydrothermal reaction temperature is 120-140℃, and the time is 3-5h.
[0018] As a further improvement of the present invention, the mass ratio of scopolamine, tropicamide and modified halloysite nanotubes in step S2 is 1:0.5-1:5:3-5.
[0019] As a further improvement of the present invention, the mass ratio of the loaded nanotubes, osmotic pressure regulator and preservative in step S3 is 10:2-3:0.01-0.015.
[0020] The present invention further protects the use of the above-described pharmaceutical composition for treating pseudomyopia in the preparation of a medicament for treating pseudomyopia.
[0021] The present invention has the following beneficial effects:
[0022] This invention relates to a compound eye drop containing scopolamine and tropicamide. The active ingredients, scopolamine hydrobromide and tropicamide hydrobromide, are extracted from plants and crystallized into salts. The compound eye drop is effective, has few side effects, is of stable quality, and is easy to store and use, providing the market with a better option for treating pseudomyopia.
[0023] This invention utilizes halloysite nanotubes with a hyaluronic acid-tannic acid-cyclodextrin complex loaded on the surface to form a sustained-release gel layer. This layer contains abundant active groups such as hydroxyl and carboxyl groups, as well as cavities of cyclodextrin, which can effectively load the active components scopolamine and tropicamide, resulting in a sustained-release effect. This allows for the slow release of active components over a long period, thus achieving a long-lasting and slow therapeutic effect and avoiding the problem of poor efficacy with a single administration. Attached Figure Description
[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0025] Figure 1 This is a comparison chart of the wrapping rates in Test Example 1;
[0026] Figure 2 This is a comparison chart of drug loading rates in Test Example 1;
[0027] Figure 3 This is a comparison chart of the rate of change of refractive power in test example 2. Detailed Implementation
[0028] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Example 1
[0029] This embodiment provides a method for preparing a pharmaceutical composition for treating pseudomyopia, comprising the following steps:
[0030] S1. Add 10g halloysite nanotubes to 300mL of water, add 4g hyaluronic acid, 2g tannic acid and 3g cyclodextrin, add 0.2g Tris-HCl solution with pH 8, and hydrothermally react at 120℃ for 3h. Centrifuge, wash and dry to obtain modified halloysite nanotubes.
[0031] S2. Dissolve 1g of scopolamine and 0.5g of tropicamide in 100mL of water, add 3g of modified halloysite nanotubes, stir and mix for 15min, centrifuge, wash, and dry to obtain loaded nanotubes.
[0032] S3. Add 10g of loaded nanotubes to 100mL of water for injection, add buffer to adjust the pH to 5.0, add 2g of potassium chloride and 0.01g of benzalkonium chloride, add water for injection to the full volume, sterilize and dispense to obtain a drug composition for treating pseudomyopia. Example 2
[0033] This embodiment provides a method for preparing a pharmaceutical composition for treating pseudomyopia, comprising the following steps:
[0034] S1. Add 15g halloysite nanotubes to 300mL of water, add 6g of hyaluronic acid, 3g of tannic acid and 5g of cyclodextrin, add 0.5g of Tris-HCl solution with pH 9, and hydrothermally react at 140℃ for 5h. Centrifuge, wash and dry to obtain modified halloysite nanotubes.
[0035] S2. Dissolve 1g of scopolamine and 1g of tropicamide in 100mL of water, add 5g of modified halloysite nanotubes, stir and mix for 15min, centrifuge, wash, and dry to obtain loaded nanotubes.
[0036] S3. Add 10g of loaded nanotubes to 100mL of water for injection, add buffer to adjust the pH to 7.0, add 3g of potassium chloride and 0.015g of benzalkonium chloride, add water for injection to the full volume, sterilize and dispense to obtain a drug composition for treating pseudomyopia. Example 3
[0037] This embodiment provides a method for preparing a pharmaceutical composition for treating pseudomyopia, comprising the following steps:
[0038] S1. Add 12g halloysite nanotubes to 300mL of water, add 5g of hyaluronic acid, 2.5g of tannic acid and 4g of cyclodextrin, add 0.35g of Tris-HCl solution with pH 8.5, and hydrothermally react at 130℃ for 4h. Centrifuge, wash and dry to obtain modified halloysite nanotubes.
[0039] S2. Dissolve 1g of scopolamine and 0.7g of tropicamide in 100mL of water, add 4g of modified halloysite nanotubes, stir and mix for 15min, centrifuge, wash, and dry to obtain loaded nanotubes.
[0040] S3. Add 10g of loaded nanotubes to 100mL of water for injection, add buffer to adjust the pH to 6.0, add 2.5g of sodium chloride and 0.012g of benzalkonium chloride, add water for injection to the total volume, sterilize and dispense to obtain a pharmaceutical composition for treating pseudomyopia.
[0041] Comparative Example 1
[0042] The difference from Example 3 is that scopolamine was not added in step S2.
[0043] Specifically as follows:
[0044] S1. Add 12g halloysite nanotubes to 300mL of water, add 5g of hyaluronic acid, 2.5g of tannic acid and 4g of cyclodextrin, add 0.35g of Tris-HCl solution with pH 8.5, and hydrothermally react at 130℃ for 4h. Centrifuge, wash and dry to obtain modified halloysite nanotubes.
[0045] S2. Dissolve 1.7g tropicamide in 100mL of water, add 4g modified halloysite nanotubes, stir and mix for 15min, centrifuge, wash, and dry to obtain loaded nanotubes.
[0046] S3. Add 10g of loaded nanotubes to 100mL of water for injection, add buffer to adjust the pH to 6.0, add 2.5g of sodium chloride and 0.012g of benzalkonium chloride, add water for injection to the total volume, sterilize and dispense to obtain a pharmaceutical composition for treating pseudomyopia.
[0047] Comparative Example 2
[0048] The difference from Example 3 is that tropicamide was not added in step S2.
[0049] Specifically as follows:
[0050] S1. Add 12g halloysite nanotubes to 300mL of water, add 5g of hyaluronic acid, 2.5g of tannic acid and 4g of cyclodextrin, add 0.35g of Tris-HCl solution with pH 8.5, and hydrothermally react at 130℃ for 4h. Centrifuge, wash and dry to obtain modified halloysite nanotubes.
[0051] S2. Dissolve 1.7g of scopolamine in 100mL of water, add 4g of modified halloysite nanotubes, stir and mix for 15min, centrifuge, wash, and dry to obtain loaded nanotubes;
[0052] S3. Add 10g of loaded nanotubes to 100mL of water for injection, add buffer to adjust the pH to 6.0, add 2.5g of sodium chloride and 0.012g of benzalkonium chloride, add water for injection to the total volume, sterilize and dispense to obtain a pharmaceutical composition for treating pseudomyopia.
[0053] Comparative Example 3
[0054] The difference from Example 3 is that no modified halloysite nanotubes were added in step S2.
[0055] Specifically as follows:
[0056] Dissolve 1g of scopolamine and 0.7g of tropicamide in 100mL of water for injection, add buffer to adjust the pH to 6.0, add 2.5g of sodium chloride and 0.012g of benzalkonium chloride, add water for injection to the total volume, sterilize and dispense to obtain a pharmaceutical composition for treating pseudomyopia.
[0057] Test Example 1
[0058] Accurately weigh 10 mg of the nanotube-loaded sample prepared in Examples 1-3 or Comparative Examples 1-2 and add it to 10 mL of 0.1 mol / L acetic acid aqueous solution. Sonicate for 5 min, centrifuge at high speed, filter the supernatant, and measure its absorbance using a UV / Vis spectrophotometer. Calculate the drug content adsorbed on the microsphere surface based on the linear regression equation of the drug's standard absorption curve. Add the centrifuged residue back to 10 mL of 0.1 mol / L acetic acid aqueous solution, seal and store at 4°C for 24 h, and then measure its absorbance at the same wavelength to calculate the drug content encapsulated within the microspheres.
[0059] The encapsulation efficiency of the drug microspheres is:
[0060] Encapsulation rate (%) = (mass of drug / theoretical mass of drug in loaded nanotubes) × 100%;
[0061] Drug loading rate (%) = (mass of drug / mass of gelatin drug microspheres) × 100%.
[0062] The results are as follows Figure 1 and 2 As shown in the figure, the loaded nanotubes prepared in Examples 1-3 of this invention have high encapsulation efficiency and drug loading efficiency.
[0063] Test Example 2
[0064] New Zealand white rabbits (less than 2 weeks old) were selected for pharmacological efficacy experiments on a myopia model. A visual deprivation myopia model was created by suturing the eyelids.
[0065] Model making: Levofloxacin eye drops were administered two days prior to surgery to prevent infection. On the day of surgery, a standard intravenous injection of a mixture of salbutamol and domidine (each milliliter of the mixture contains 0.5 mg of domidine and 50 mg of salbutamol) was given. The anesthetized New Zealand white rabbit was placed on its side on the operating table. The conjunctival sacs of both eyes were irrigated and disinfected. The upper eyelid was lifted with forceps in the left hand, and ophthalmic scissors were used in the right hand to cut from the inner canthus 2-3 mm from the eyelid margin towards the outer canthus. The lower eyelid was treated in the same way. The upper and lower eyelids were then sutured together. Tobramycin and dexamethasone eye drops were administered for three consecutive days postoperatively. The eyelid sutures were checked daily after surgery, and any sutures that had come loose were immediately re-sutured.
[0066] Eight weeks after modeling, spherical refractive power data were collected using a HandyRey-K fully automated refractometer. Animals with an average spherical refractive power value of less than 2.75D in both eyes were selected based on the spherical refractive power results and randomly divided into 7 groups: control group, Examples 1-3, and Comparative Examples 1-3, with 6 animals in each group. The enrolled animals were given eye drops of the drug composition for treating pseudomyopia prepared in Examples 1-3 or Comparative Examples 1-3, with physiological saline as the control group. The dose was 0.1 mL once a day for four weeks. Spherical refractive power was measured on Day 1, Day 8, Day 15, Day 22, and Day 29 after the first dose.
[0067] Spherical refractive power measurement: Animals were transferred from indoor lighting conditions to the ophthalmic laboratory operating room, and six measurements were taken using an optician in infrared mode, with the average value recorded. Spherical refractive power was measured at different time points, and the rate of change in refractive power (%) was calculated.
[0068] See results Figure 3 As shown in the figure, the drug compositions for treating pseudomyopia prepared in Examples 1-3 of this invention have a significant effect on improving myopia. Comparative Examples 1-2 are single-drug administration, and their effects are significantly reduced. Comparative Example 3 does not contain modified halloysite nanotubes and does not have a sustained-release drug effect, so its therapeutic effect is also significantly reduced.
[0069] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A pharmaceutical composition for treating pseudomyopia, characterized in that, The pharmaceutical composition comprises scopolamine or a pharmaceutically acceptable salt thereof, and tropicamide or a pharmaceutically acceptable salt thereof, wherein the mass ratio of scopolamine to tropicamide is 1:0.5 to 1:
1. The preparation method includes the following steps: S1. Halloysite nanotubes are added to water, along with hyaluronic acid, tannic acid, and cyclodextrin, and a catalyst. The mixture is subjected to a hydrothermal reaction, centrifuged, washed, and dried to obtain modified halloysite nanotubes. The mass ratio of halloysite nanotubes, hyaluronic acid, tannic acid, cyclodextrin, and catalyst is 10-15:4-6:2-3:3-5:0.2-0.
5. S2. Scopolamine and tropicamide were dissolved in water, modified halloysite nanotubes were added, the mixture was stirred and mixed evenly, centrifuged, washed and dried to obtain loaded nanotubes; S3. Add the loaded nanotubes to water for injection, add a pH adjuster to adjust the pH to 5.0-7.0, add an osmotic pressure regulator and a preservative, add water for injection to the total volume, sterilize, and dispense to obtain a pharmaceutical composition for treating pseudomyopia; the mass ratio of the loaded nanotubes, osmotic pressure regulator and preservative is 10:2-3:0.01-0.
015.
2. The pharmaceutical composition for treating pseudomyopia according to claim 1, characterized in that, The pH adjuster is a boric acid-borax buffer system, which adjusts the pH value to 5.0-7.
0.
3. The pharmaceutical composition for treating pseudomyopia according to claim 1, characterized in that, The osmotic pressure regulator is potassium chloride or sodium chloride; the preservative is benzalkonium chloride.
4. The pharmaceutical composition for treating pseudomyopia according to claim 1, characterized in that, The catalyst in step S1 is a Tris-HCl solution with a pH of 8-9, and the hydrothermal reaction is carried out at a temperature of 120-140℃ for 3-5 hours.
5. Use of a pharmaceutical composition for treating pseudomyopia as described in any one of claims 1-4 in the preparation of a medicament for treating pseudomyopia.