Method for preparing drug-loaded contact lenses based on supercritical impregnation
By using supercritical fluid impregnation technology to co-load drugs and eye-care essential oils into contact lenses, the problems of insufficient drug loading and uneven distribution are solved, achieving high drug loading and uniform distribution, improving drug efficacy and wearing comfort, while avoiding organic solvent residue.
Patent Information
- Application Number
- CN202510877519.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-27
- Publication Date
- 2025-10-28
AI Technical Summary
Existing drug-eluting contact lenses suffer from problems such as limited drug loading capacity, uneven drug distribution, short release time, and organic solvent residue.
Using supercritical impregnation technology, the drug and eye-care essential oil are placed together in a reaction vessel, and carbon dioxide is introduced to form supercritical carbon dioxide. Utilizing its high solubility and permeability, the drug and essential oil are evenly penetrated into the lens. The drug and essential oil are released into the lens through pressure release.
It significantly improves the drug loading capacity and drug distribution uniformity of the lens, avoids organic solvent residue, enhances the efficacy of the drug, and improves wearing comfort.
Smart Images
Figure CN120837548A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a method for preparing drug-loaded contact lenses based on supercritical impregnation. Background Technology
[0002] Contact lenses, a commonly used vision correction tool, are primarily composed of polymer materials. Due to their advantages such as comfort, wide field of vision, and improved appearance, they are widely used by various groups of people. In recent years, with technological advancements, drug-loaded contact lenses have emerged as an innovative treatment method. Drug-loaded contact lenses release medication directly and slowly into the eye, effectively improving local conditions and enhancing drug bioavailability, particularly showing significant efficacy in treating chronic eye diseases, eye infections, and dry eye syndrome.
[0003] Currently, the most common methods for manufacturing drug-eluting contact lenses are impregnation and hydrogel drug delivery systems. Impregnation involves immersing the contact lens in a drug solution, allowing the drug to diffuse into the lens material. This method is simple and low-cost, but suffers from limitations such as limited drug loading capacity, uneven distribution, and short release time. Hydrogel systems, on the other hand, rely on the lens's high water content to encapsulate the drug, offering good biocompatibility and comfort. However, they are more expensive, have less uniform drug distribution within the lens, and still face challenges in achieving slow and sustained drug release. Summary of the Invention
[0004] Purpose of the invention: The purpose of this invention is to provide a method for preparing drug-loaded contact lenses that can significantly increase the drug loading capacity of the lens while leaving no organic solvent residue in the lens matrix.
[0005] Technical solution: The method for preparing drug-loaded contact lenses based on supercritical impregnation according to the present invention includes the following steps:
[0006] (1) Place the medicine, eye-care essential oil and contact lenses with dialysis bags into the reaction vessel. After sealing the reaction vessel, introduce carbon dioxide into the reaction vessel to expel the air.
[0007] (2) Continue to introduce carbon dioxide into the reactor while starting stirring and heating. Stop introducing carbon dioxide when the temperature and pressure inside the reactor reach the predetermined values. After impregnation is completed, slowly depressurize to release carbon dioxide and obtain drug-loaded contact lenses.
[0008] In step (1), the contact lens material includes polyhydroxyethyl methacrylate (P-HEMA), polyacrylate (PAA), polyvinyl alcohol (PVA), polyacrylic acid (PAA) and hydrogel complex, HEMA and methacrylic acid (MAA) copolymer, and methyl methacrylate (MMA) hydrogel. The drug is at least one of gatifloxacin, ciprofloxacin, tobramycin, levofloxacin, acyclovir, valacyclovir, dexamethasone, fluorometholone, loratadine, beclometasone, fluconazole, or amphotericin B. The eye-benefiting essential oil is at least one of cassia seed essential oil, chamomile essential oil, or lavender essential oil.
[0009] In step (1), the mass ratio of contact lens to drug is 1:0.1 to 0.3, preferably 1:0.2; the mass ratio of contact lens to essential oil is 1:0.01 to 0.05, preferably 1:0.05.
[0010] In step (1), the carbon dioxide is introduced for 1 to 15 minutes; preferably 5 minutes.
[0011] In step (2), the volume of carbon dioxide introduced into the reactor is 10 mL to 10-30 mg of the contact lens; preferably 10 mL to 20 mg.
[0012] In step (2), the temperature inside the reactor is 40-60℃ and the pressure is 16-20MPa. Under these temperature and pressure conditions, carbon dioxide forms supercritical carbon dioxide inside the reactor. The impregnation time is 1-6h, preferably 3h. The depressurization rate is 1-5MPa / min, preferably 3MPa / min.
[0013] In this invention, under corresponding temperature and pressure, supercritical carbon dioxide is formed in the reactor. Drug molecules and essential oil molecules dissolve in the supercritical carbon dioxide. After the supercritical carbon dioxide carries the drug molecules and essential oil molecules into the contact lens, carbon dioxide gas is released through depressurization to obtain a drug-loaded contact lens.
[0014] This invention employs supercritical carbon dioxide impregnation technology to co-load medication and eye-care essential oil into contact lenses. On one hand, eye-care essential oil, as a natural plant extract, possesses beneficial effects such as anti-inflammatory and antioxidant properties. Low concentrations of eye-care essential oil can alleviate symptoms like eye fatigue and dryness, positively impacting eye health. Therefore, when eye-care essential oil and medication are co-loaded into contact lenses, their synergistic effect enhances the therapeutic efficacy of the medication and improves eye comfort and health. On the other hand, eye-care essential oil has excellent solubility and permeability in supercritical carbon dioxide, significantly increasing the solubility and permeability of the medication within it. This allows more medication to dissolve in supercritical carbon dioxide, thereby promoting greater drug impregnation into the lens and increasing the drug loading capacity of the contact lens. Furthermore, this method also promotes uniform drug distribution within the lens matrix.
[0015] Beneficial effects: Compared with the prior art, the present invention has the following significant advantages: (1) The method of the present invention can effectively avoid the problem of organic solvent residue in the traditional solvent method; (2) The high solubility and permeability of supercritical carbon dioxide can enable drugs and essential oils to penetrate evenly into the contact lens matrix, significantly improving the drug loading capacity and drug distribution uniformity of the lens; at the same time, the synergistic effect of essential oils can further improve the drug loading capacity and drug distribution uniformity of the lens by effectively improving the solubility of drugs in supercritical carbon dioxide and the diffusion in the lens; (3) The synergistic effect of essential oils can enhance the efficacy of drugs and improve eye comfort when wearing contact lenses. Attached Figure Description
[0016] Figure 1 UV absorbance analysis of gatifloxacin aqueous solution;
[0017] Figure 2 Image of a contact lens obtained after supercritical carbon dioxide impregnation treatment. Detailed Implementation
[0018] Example 1
[0019] This invention relates to a method for preparing drug-loaded contact lenses based on supercritical impregnation, comprising the following steps:
[0020] (1) Place the polyhydroxyethyl methacrylate (P-HEMA) matrix contact lens into a dialysis bag, one lens per dialysis bag, with each lens weighing 100mg; place 20mg gatifloxacin, 5mg cassia seed essential oil and one contact lens from the dialysis bag into a reaction vessel (impregnation vessel), seal the reaction vessel, and introduce carbon dioxide into the reaction vessel to purge the air from the system; the introduction time is 5min.
[0021] (2) Continue to introduce carbon dioxide and heat it. When the temperature inside the reactor reaches 40°C and the pressure reaches 16MPa, stop introducing carbon dioxide. The volume ratio of the introduced carbon dioxide to the volume of the contact lens is 10mL:20mg. Under the above temperature and pressure, carbon dioxide forms supercritical carbon dioxide in the reactor. Start the stirring device and maintain it for 3h. Then slowly release the pressure inside the reactor at a rate of 3MPa / min to obtain the drug-loaded contact lens.
[0022] The drug loading of the drug-loaded contact lens prepared in Example 1 was determined by ultraviolet spectrophotometry, and the drug loading was 2.97 μg / 100 mg lens.
[0023] Figure 1 The test results showed that the drug was successfully loaded into the lens; Figure 2 These are lenses that have undergone supercritical carbon dioxide drug-loaded impregnation treatment, and it can be seen that the physical state of the lenses has not changed.
[0024] Example 2
[0025] This invention relates to a method for preparing drug-loaded contact lenses based on supercritical impregnation, comprising the following steps:
[0026] (1) Place the polyacrylate (PAA) matrix contact lens into a dialysis bag, one lens per dialysis bag, with each lens weighing 100mg; place 10mg ciprofloxacin, 2mg chamomile essential oil and one contact lens from the dialysis bag into a reaction vessel, seal the reaction vessel, and introduce carbon dioxide into the reaction vessel to purge the air from the system; the introduction time is 1min.
[0027] (2) Continue to introduce carbon dioxide and heat it. When the temperature inside the reactor reaches 50°C and the pressure reaches 20MPa, stop introducing carbon dioxide. The volume ratio of the introduced carbon dioxide to the volume of the contact lens is 10mL:10mg. Under the above temperature and pressure, carbon dioxide forms supercritical carbon dioxide in the reactor. Start the stirring device and maintain it for 1 hour. Then slowly release the pressure inside the reactor at a rate of 5MPa / min to obtain the drug-loaded contact lens.
[0028] The drug loading of the drug-loaded contact lens prepared in Example 2 was determined by ultraviolet spectrophotometry, and the drug loading was 2.42 μg / 100 mg lens.
[0029] Example 3
[0030] This invention relates to a method for preparing drug-loaded contact lenses based on supercritical impregnation, comprising the following steps:
[0031] (1) Place the polyvinyl alcohol (PVA) matrix contact lens into a dialysis bag, one lens per dialysis bag, with each lens weighing 100mg; place 30mg of levofloxacin, 1mg of cassia seed essential oil and one contact lens from the dialysis bag into a reaction vessel (impregnation vessel), seal the reaction vessel, and introduce carbon dioxide into the reaction vessel to purge the air from the system; the introduction time is 15min;
[0032] (2) Continue to introduce carbon dioxide and heat it. When the temperature inside the reactor reaches 60°C and the pressure reaches 20MPa, stop introducing carbon dioxide. The volume ratio of the introduced carbon dioxide to the volume of the contact lens is 10mL:30mg. Under the above temperature and pressure, carbon dioxide forms supercritical carbon dioxide in the reactor. Start the stirring device and maintain it for 6h. Then slowly release the pressure inside the reactor at a rate of 1MPa / min to obtain the drug-loaded contact lens.
[0033] The drug loading of the drug-loaded contact lens prepared in Example 3 was determined by ultraviolet spectrophotometry, and the drug loading was 2.63 μg / 100 mg lens.
[0034] Comparative Example 1
[0035] The only difference between Comparative Example 1 and Example 1 is that 5 mg of cassia seed essential oil was not added in step (1). Specifically:
[0036] (1) Place the polyhydroxyethyl methacrylate (P-HEMA) matrix contact lens into a dialysis bag, one lens per dialysis bag, and the weight of each lens is 100mg; put 20mg gatifloxacin and one contact lens in the dialysis bag into the reaction vessel, seal the reaction vessel, and introduce carbon dioxide into the reaction vessel to purge the air in the system; the introduction time is 5min;
[0037] (2) Continue to introduce carbon dioxide and heat it. When the temperature inside the reactor reaches 40°C and the pressure reaches 16MPa, stop introducing carbon dioxide. The volume ratio of the introduced carbon dioxide to the volume of the contact lens is 10mL:20mg. Under the above temperature and pressure, carbon dioxide forms supercritical carbon dioxide in the reactor. Start the stirring device and maintain it for 3h. Then slowly release the pressure inside the reactor at a rate of 3MPa / min to obtain the drug-loaded contact lens.
[0038] The drug loading of the drug-loaded contact lens prepared in Comparative Example 1 was determined by ultraviolet spectrophotometry, and the drug loading was 2.27 μg / 100 mg lens.
[0039] Comparative Example 2
[0040] The only difference between Comparative Example 2 and Example 1 is that 10 mg of cassia seed essential oil was added in step (1), specifically:
[0041] (1) Place the polyhydroxyethyl methacrylate (P-HEMA) matrix contact lens into a dialysis bag, one lens per dialysis bag, with each lens weighing 100mg; place 20mg gatifloxacin, 10mg cassia seed essential oil and one contact lens from the dialysis bag into a reaction vessel, seal the reaction vessel, and introduce carbon dioxide into the reaction vessel to purge the air from the system; the introduction time is 5min.
[0042] (2) Continue to introduce carbon dioxide and heat it. When the temperature inside the reactor reaches 40°C and the pressure reaches 16MPa, stop introducing carbon dioxide. The volume ratio of the introduced carbon dioxide to the volume of the contact lens is 10mL:20mg. Under the above temperature and pressure, carbon dioxide forms supercritical carbon dioxide in the reactor. Start the stirring device and maintain it for 3h. Then slowly release the pressure inside the reactor at a rate of 3MPa / min to obtain the drug-loaded contact lens.
[0043] The drug loading of the drug-loaded contact lens prepared in Comparative Example 2 was determined by ultraviolet spectrophotometry, and the drug loading was 2.79 μg / 100 mg lens.
[0044] Comparative Example 3
[0045] The only difference between Comparative Example 3 and Example 1 is that in step (2), the pressure inside the reactor was slowly released at a rate of 10 MPa / min. Specifically:
[0046] (1) Place the polyhydroxyethyl methacrylate (P-HEMA) matrix contact lens into a dialysis bag, one lens per dialysis bag, with each lens weighing 100mg; place 20mg gatifloxacin, 5mg cassia seed essential oil and one contact lens from the dialysis bag into a reaction vessel, seal the reaction vessel, and introduce carbon dioxide into the reaction vessel to purge the air from the system; the introduction time is 5min.
[0047] (2) Continue to introduce carbon dioxide and heat it. When the temperature inside the reactor reaches 40°C and the pressure reaches 16MPa, stop introducing carbon dioxide. The volume ratio of the introduced carbon dioxide to the volume of the contact lens is 10mL:20mg. Under the above temperature and pressure, carbon dioxide forms supercritical carbon dioxide in the reactor. Start the stirring device and maintain it for 3 hours. Then slowly release the pressure inside the reactor at a rate of 10MPa / min to obtain the drug-loaded contact lens.
[0048] The drug loading of the drug-loaded contact lens prepared in Comparative Example 3 was determined by ultraviolet spectrophotometry, and the drug loading was 2.43 μg / 100 mg lens.
[0049] Comparative Example 4
[0050] The only difference between Comparative Example 4 and Example 1 is that the volume ratio of carbon dioxide introduced in step (2) to the volume-to-mass ratio of the contact lens is 10 mL: 50 mg.
[0051] (1) Place the polyhydroxyethyl methacrylate (P-HEMA) matrix contact lens into a dialysis bag, one lens per dialysis bag, with each lens weighing 100mg; place 20mg gatifloxacin, 5mg cassia seed essential oil and one contact lens from the dialysis bag into a reaction vessel, seal the reaction vessel, and introduce carbon dioxide into the reaction vessel to purge the air from the system; the introduction time is 5min.
[0052] (2) Continue to introduce carbon dioxide and heat it. When the temperature inside the reactor reaches 40°C and the pressure reaches 16MPa, stop introducing carbon dioxide. The volume ratio of the introduced carbon dioxide to the volume of the contact lens is 10mL:50mg. Under the above temperature and pressure, carbon dioxide forms supercritical carbon dioxide in the reactor. Start the stirring device and maintain it for 3h. Then slowly release the pressure inside the reactor at a rate of 3MPa / min to obtain the drug-loaded contact lens.
[0053] The drug loading of the drug-loaded contact lens prepared in Comparative Example 4 was determined by ultraviolet spectrophotometry, and the drug loading was 2.59 μg / 100 mg lens.
Claims
1. A method for preparing drug-loaded contact lenses based on supercritical impregnation, characterized in that, The steps include: (1) Place the medicine, eye-care essential oil and contact lenses with dialysis bags into the reaction vessel. After sealing the reaction vessel, introduce carbon dioxide into the reaction vessel to expel the air. (2) Continue to introduce carbon dioxide into the reactor while starting stirring and heating. Stop introducing carbon dioxide when the temperature and pressure inside the reactor reach the predetermined values. After impregnation is completed, slowly depressurize to release carbon dioxide and obtain drug-loaded contact lenses.
2. The method according to claim 1, characterized in that: In step (1), the drug is at least one of gatifloxacin, ciprofloxacin, topiramate, levofloxacin, acyclovir, valacyclovir, dexamethasone, fluchlorothiazide, loratadine, beclomethasone, fluconazole, or amphotericin B.
3. The method according to claim 1, characterized in that: In step (1), the eye-benefiting essential oil is at least one of cassia seed essential oil, chamomile essential oil, or lavender essential oil.
4. The method according to claim 1, characterized in that: In step (1), the mass ratio of the contact lens to the drug is 1:0.1 to 0.
3.
5. The method according to claim 1, characterized in that: In step (1), the mass ratio of the contact lens to the essential oil is 1:0.01 to 0.
05.
6. The method according to claim 1, characterized in that: In step (1), the carbon dioxide is introduced for 1 to 15 minutes.
7. The method according to claim 1, characterized in that: In step (2), the volume of carbon dioxide introduced into the reactor is 10 mL to 10-30 mg of contact lens.
8. The method according to claim 1, characterized in that: In step (2), the temperature inside the reactor is 40-60℃ and the pressure is 16-20MPa. Under these temperature and pressure conditions, carbon dioxide forms supercritical carbon dioxide inside the reactor.
9. The method according to claim 1, characterized in that: In step (2), the soaking time is 1 to 6 hours; the pressure relief rate is 1 to 5 MPa / min.