A compound eye drop containing PDRN and a preparation method thereof
Patent Information
- Application Number
- CN202611272095.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-08-20
- Publication Date
- 2026-10-13
AI Technical Summary
[0005]有鉴于此，本发明提供了一种含PDRN的复方滴眼液及其制备方法，以解决现有滴眼液的眼表滞留时间短、PDRN易降解失活、修复效果差的问题
1、本发明通过非离子型增稠剂与透明质酸钠的协同复配，构建了具有适度黏度和黏膜黏附性的眼用凝胶网络体系。透明质酸钠不仅自身具有优良的保湿和黏附性能，还能与增稠剂分子间形成氢键等非共价相互作用，进一步增强凝胶网络的致密性和抗泪液冲刷能力。同时，非离子型等渗剂的加入在调节渗透压的同时，可辅助提高体系的铺展性和角膜接触角，使滴眼液滴入眼表后能够均匀铺展并持久滞留。上述组分协同作用，使得本发明所述滴眼液在眼表的半衰期显著延长，每日用药次数也显著减少，明显提高了患者的依从性；
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Abstract
Description
Technical Field
[0001] This invention relates to the field of eye drop technology, and more particularly to a compound eye drop containing PDRN and its preparation method. Background Technology
[0002] Polydeoxyribonucleotides (PDRNs) are a class of bioactive polynucleotide mixtures derived from fish germ cells such as salmon testes. They possess excellent tissue repair activity and extremely low immunogenicity, exhibiting good biocompatibility. Research reports and clinical results show that PDRNs have significant repair and regeneration effects on various tissue injuries, including skin wounds, corneal damage, gastrointestinal mucosal damage, and bone injuries, making them suitable for a wide range of applications. The repair mechanism of PDRNs primarily involves their degradation product, adenosine, activating the adenosine A2A receptor pathway, thereby promoting the expression of repair-related factors such as vascular endothelial growth factor (VEGF), and facilitating the repair and regeneration of damaged tissues. Based on this mechanism, the application of PDRNs in ophthalmology is receiving increasing attention, particularly offering new insights for the treatment of ocular surface diseases such as dry eye and corneal epithelial damage.
[0003] Eye drops are currently the most commonly used and convenient method of drug administration in the treatment of ophthalmic diseases. However, traditional eye drops face a series of inherent drawbacks. On the one hand, due to the presence of the tear film barrier and the effects of tear flushing and nasolacrimal duct metabolism caused by frequent blinking, solution-type eye drops generally suffer from insufficient ocular retention time, poor sustained drug effect, low absorption, and the need for frequent administration. Studies have shown that after conventional eye drops are instilled into the ocular surface, most of the drug leaves the anterior corneal region with the tear fluid within 2 minutes, resulting in extremely low bioavailability. To maintain an effective drug concentration, patients usually need to administer the medication multiple times a day, which not only leads to poor patient compliance but also increases the risk of potential side effects. On the other hand, large-molecule nucleic acid active ingredients, such as PDRN, have poor stability in eye drop formulations. In solution, they are easily degraded and inactivated by factors such as temperature, pH, and enzyme degradation, resulting in insufficient storage stability and limiting their practical application in ophthalmic formulations. In addition, existing ocular surface repair eye drops generally suffer from a single mechanism of action and lack a formulation design approach that leverages the synergistic effects of multiple components. They can only exert their repair effects through a single pathway and cannot comprehensively improve ocular surface damage, tear film homeostasis disorders, and other problems, resulting in limited therapeutic efficacy.
[0004] Therefore, it is of great significance to develop a compound eye drop that can significantly prolong the ocular surface retention time, protect the biological activity of PDRN, and has the synergistic effect of multiple components. Summary of the Invention
[0005] In view of this, the present invention provides a compound eye drop containing PDRN and its preparation method, in order to solve the problems of short ocular surface retention time, easy degradation and inactivation of PDRN, and poor repair effect of existing eye drops.
[0006] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides a compound eye drop containing PDRN, comprising the following components by mass percentage: PDRN 0.05~1.0%, Sodium Hyaluronate 0.05~0.5%, Nicotinamide 0.05~1.0%, Amino Acid Mixture 0.01~0.5%, Small Molecule Oligopeptide 0.001~0.1%, Nonionic Thickener 0.1~1.0%, Nonionic Isotonic Agent 2.0~6.0%, Polyurethane Biguanide 0.0001~0.0015%, Balance: Water; The pH value of the compound eye drops containing PDRN is 6.5~7.5.
[0007] Preferably, the amino acid mixture is obtained by mixing glycine, proline, hydroxyproline, valine, leucine, lysine, serine and cysteine.
[0008] Preferably, the mass ratio of glycine, proline, hydroxyproline, valine, leucine, lysine, serine, and cysteine is 1:0.7~0.8:0.35~0.45:0.4~0.52:0.12~0.18:0.08~0.12:0.08~0.12:0.04~0.08.
[0009] Preferably, the small molecule oligopeptide includes one or more of palmitoyl tetrapeptide-7, acetyl hexapeptide-8, and copper tripeptide-1.
[0010] Preferably, the nonionic thickener includes one or more of hydroxypropyl methylcellulose, hydroxypropyl ethylcellulose, polyvinylpyrrolidone, poloxamer 188, and poloxamer 407.
[0011] Preferably, the nonionic isotonic agent includes one or more of glycerol, sorbitol, mannitol and polyethylene glycol.
[0012] Preferably, the PDRN-containing compound eye drops further include a pH adjuster, which includes one or more of boric acid, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, and sodium dihydrogen phosphate.
[0013] The present invention also provides a method for preparing the above-mentioned PDRN-containing compound eye drops, comprising the following steps: 1) Mix nonionic thickener, nonionic isotonic agent and some water, heat to dissolve, cool to room temperature, add sodium hyaluronate, nicotinamide and amino acid mixture, and then adjust the pH of the system to 6.5~7.5 to obtain pre-mixed solution; 2) Mix the pre-mixed solution, PDRN, small molecule oligopeptide, polyaminopropyl biguanide and the remaining water, and then adjust the pH of the system to 6.5~7.5 to obtain compound eye drops containing PDRN.
[0014] Preferably, the heating and dissolving temperature in step 1) is 70~80℃; the mass ratio of the partial water in step 1) to the remaining water in step 2) is 3~4:1~2; and the mixing temperature in step 2) is 20~30℃.
[0015] Preferably, the pH adjuster used in step 1) and the pH adjuster used in step 2) independently include one or more of boric acid, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, and sodium dihydrogen phosphate.
[0016] As can be seen from the above technical solution, compared with the prior art, the beneficial effects of the present invention are as follows: 1. This invention constructs an ophthalmic gel network system with moderate viscosity and mucosal adhesion through the synergistic combination of a nonionic thickener and sodium hyaluronate. Sodium hyaluronate not only possesses excellent moisturizing and adhesive properties but also forms non-covalent interactions such as hydrogen bonds with the thickener molecules, further enhancing the density of the gel network and its resistance to tear erosion. Simultaneously, the addition of a nonionic isotonic agent adjusts the osmotic pressure and helps improve the system's spreadability and corneal contact angle, allowing the eye drops to spread evenly and remain in place on the ocular surface for a prolonged period. The synergistic effect of these components significantly prolongs the half-life of the eye drops on the ocular surface, significantly reduces the frequency of daily administration, and substantially improves patient compliance. 2. The eye drops of this invention use only non-ionic excipients, avoiding aggregation or conformational changes induced by electrostatic interactions between ionic excipients and PDRN, thus protecting the structural integrity of PDRN from the source. Secondly, this invention uses polyaminopropyl biguanide as a preservative, which has a much lower destructive effect on nucleic acid macromolecules than traditional preservatives, effectively inhibiting bacteria while minimizing damage to PDRN. Thirdly, the preparation method of the eye drops of this invention pre-adjusts the pH of the pre-mixed solution to 6.5-7.5 before adding PDRN and small molecule oligopeptides, ensuring that the active ingredients are in a stable weakly acidic to neutral environment from the beginning of dissolution, avoiding degradation caused by subsequent significant pH adjustments; simultaneously, the dissolution temperature of the active ingredients is strictly controlled at 20-30℃, further protecting the heat sensitivity of PDRN and oligopeptides. Through the above synergistic effects, the PDRN in the eye drops of this invention is not easily degraded or inactivated, exhibiting excellent storage stability. 3. This invention achieves a synergistic effect by adding a mixture of PDRN, small molecule oligopeptides, nicotinamide, and amino acids. PDRN degrades to produce adenosine, activating A2A receptors, promoting the expression of repair factors such as VEGF, and accelerating angiogenesis and granulation tissue formation. Small molecule oligopeptides directly bind to cell membrane surface receptors, promoting corneal epithelial cell proliferation, migration, and matrix metalloproteinase regulation, accelerating wound re-epithelialization. Nicotinamide, as an NAD+ receptor... + The precursor enhances cellular energy metabolism, inhibits the release of inflammatory factors, and reduces corneal inflammation. The amino acid mixture provides the core amino acid raw materials required for collagen synthesis. In summary, this invention achieves multi-target synergistic repair through a quadruple repair network of PDRN, small molecule oligopeptides, nicotinamide, and amino acid mixture, which greatly improves the repair effect of the eye drops described in this invention and has significant clinical practical value and socio-economic benefits. Detailed Implementation
[0017] This invention provides a compound eye drop containing PDRN, preferably comprising the following components in the indicated mass percentages: PDRN 0.05-1.0%, sodium hyaluronate 0.05-0.5%, nicotinamide 0.05-1.0%, amino acid mixture 0.01-0.5%, small molecule oligopeptide 0.001-0.1%, nonionic thickener 0.1-1.0%, nonionic isotonic agent 2.0-6.0%, polyaminopropyl biguanide 0.0001-0.0015%, with the balance being water; more preferably comprising the following components in the indicated mass percentages: PDRN The composition comprises, more preferably, the following components by mass percentage: PDRN 0.1-0.6%, sodium hyaluronate 0.1-0.4%, nicotinamide 0.1-0.6%, amino acid mixture 0.05-0.4%, small molecule oligopeptide 0.005-0.05%, nonionic thickener 0.2-0.6%, nonionic isotonic agent 2.5-5.5%, polyaminopropyl biguanide 0.0003-0.0010%, with the balance being water.
[0018] In this invention, the pH value of the PDRN-containing compound eye drops is 6.5-7.5, preferably 6.6-7.3, more preferably 6.8-7.2, and even more preferably 7.
[0019] In this invention, the amino acid mixture is preferably obtained by mixing glycine, proline, hydroxyproline, valine, leucine, lysine, serine and cysteine.
[0020] In this invention, the preferred mass ratio of glycine, proline, hydroxyproline, valine, leucine, lysine, serine, and cysteine is 1:0.7~0.8:0.35~0.45:0.4~0.52:0.12~0.18:0.08~0.12:0.08~0.12:0.04~0.08, more preferably 1:0.72~0.78:0.38~0.42:0.42~0.5:0.13~0.16:0.09~0.11:0.09~0.11:0.05~0.07, and even more preferably 1:0.75:0.4:0.45:0.15:0.1:0.1:0.06.
[0021] In this invention, the small molecule oligopeptide preferably includes one or more of palmitoyl tetrapeptide-7, acetyl hexapeptide-8, and copper tripeptide-1.
[0022] In this invention, the nonionic thickener preferably includes one or more of hydroxypropyl methylcellulose, hydroxypropyl ethylcellulose, polyvinylpyrrolidone, poloxamer 188, and poloxamer 407.
[0023] In this invention, the nonionic isotonic agent preferably includes one or more of glycerol, sorbitol, mannitol and polyethylene glycol.
[0024] In this invention, the compound eye drops containing PDRN further include a pH adjuster, which includes one or more of boric acid, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, and sodium dihydrogen phosphate.
[0025] The present invention also provides a method for preparing the above-mentioned PDRN-containing compound eye drops, comprising the following steps: 1) Mix nonionic thickener, nonionic isotonic agent and some water, heat to dissolve, cool to room temperature, add sodium hyaluronate, nicotinamide and amino acid mixture, and then adjust the pH of the system to 6.5~7.5 to obtain pre-mixed solution; 2) Mix the pre-mixed solution, PDRN, small molecule oligopeptide, polyaminopropyl biguanide and the remaining water, and then adjust the pH of the system to 6.5~7.5 to obtain compound eye drops containing PDRN.
[0026] In this invention, the heating and dissolving temperature in step 1) is 70~80℃, preferably 72~78℃, and more preferably 75℃; the mass ratio of the partial water in step 1) to the remaining water in step 2) is 3~4:1~2, preferably 3.2~3.8:1.2~1.8, more preferably 3.3~3.7:1.3~1.7, and more preferably 3.5:1.5; the mixing temperature in step 2) is 20~30℃, preferably 22~28℃, and more preferably 25℃.
[0027] In this invention, the pH adjuster used in step 1) and the pH adjuster used in step 2) preferably independently include one or more of boric acid, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, and sodium dihydrogen phosphate.
[0028] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.
[0029] Example 1
[0030] In this embodiment, the compound eye drops containing PDRN comprise the following components by mass percentage: PDRN 0.05%, sodium hyaluronate 0.05%, nicotinamide 0.05%, an amino acid mixture (obtained by mixing glycine, proline, hydroxyproline, valine, leucine, lysine, serine, and cysteine in a mass ratio of 1:0.7:0.35:0.4:0.12:0.08:0.08:0.04) 0.01%, palmitoyl tetrapeptide-7 0.001%, hydroxypropyl methylcellulose 0.1%, glycerin 2.0%, polyurethane biguanide 0.0001%, and the balance being water; The preparation method of the above-mentioned compound eye drops containing PDRN is as follows: 1) Mix hydroxypropyl methylcellulose, glycerin and some water, heat to 70°C to dissolve, cool to room temperature, add sodium hyaluronate, nicotinamide and amino acid mixture, then add disodium hydrogen phosphate to adjust the pH of the system to 6.5 to obtain the pre-mixed solution; 2) Mix the pre-mixed solution, PDRN, palmitoyl tetrapeptide-7, polyaminopropyl biguanide and the remaining water at 20°C, wherein the mass ratio of the partial water to the remaining water is 3:2. Then add disodium hydrogen phosphate to adjust the pH of the system to 6.5 to obtain the compound eye drops containing PDRN.
[0031] Example 2
[0032] In this embodiment, the compound eye drops containing PDRN comprise the following components by mass percentage: PDRN 0.5%, sodium hyaluronate 0.3%, nicotinamide 0.3%, an amino acid mixture (obtained by mixing glycine, proline, hydroxyproline, valine, leucine, lysine, serine, and cysteine in a mass ratio of 1:0.75:0.4:0.45:0.15:0.1:0.1:0.06) 0.2%, copper tripeptide-1 0.02%, poloxamer 188 0.4%, mannitol 4.0%, polyaminopropyl biguanide 0.0006%, and the balance being water; The preparation method of the above-mentioned compound eye drops containing PDRN is as follows: 1) Mix poloxamer 188, mannitol and some water, heat to 75°C to dissolve, cool to room temperature, add sodium hyaluronate, nicotinamide and amino acid mixture, then add sodium dihydrogen phosphate to adjust the pH of the system to 7 to obtain the pre-adjusted solution; 2) Mix the pre-mixed solution, PDRN, copper tripeptide-1, polyaminopropyl biguanide and the remaining water at 25°C, wherein the mass ratio of the partial water to the remaining water is 3.5:1.5. Then add sodium dihydrogen phosphate to adjust the pH of the system to 7 to obtain the compound eye drops containing PDRN.
[0033] Example 3
[0034] In this embodiment, the compound eye drops containing PDRN comprise the following components by mass percentage: PDRN 1.0%, sodium hyaluronate 0.5%, nicotinamide 1.0%, an amino acid mixture (obtained by mixing glycine, proline, hydroxyproline, valine, leucine, lysine, serine, and cysteine in a mass ratio of 1:0.8:0.45:0.52:0.18:0.12:0.12:0.08) 0.5%, acetyl hexapeptide-8 0.1%, hydroxypropyl ethyl cellulose 1.0%, sorbitol 6.0%, polyurethane biguanide 0.0015%, and the balance being water; The preparation method of the above-mentioned compound eye drops containing PDRN is as follows: 1) Mix polyvinylpyrrolidone, sorbitol and some water, heat to 80°C to dissolve, cool to room temperature, add sodium hyaluronate, nicotinamide and amino acid mixture, then add boric acid to adjust the pH of the system to 7 to obtain the pre-adjusted solution; 2) Mix the pre-mixed solution, PDRN, acetyl hexapeptide-8, polyaminopropyl biguanide and the remaining water at 30°C, wherein the mass ratio of the partial water to the remaining water is 4:1. Then add boric acid to adjust the pH of the system to 7 to obtain the compound eye drops containing PDRN.
[0035] Comparative Example 1
[0036] The only difference between this comparative example and Example 1 is that PDRN was not added; all other components and preparation conditions remained the same.
[0037] Comparative Example 2
[0038] The only difference between this comparative example and Example 1 is that polyurethane biguanide is replaced with benzalkonium chloride, while other components and preparation conditions remain unchanged.
[0039] Comparative Example 3
[0040] The only difference between this comparative example and Example 2 is that the amino acid mixture was not added; all other components and preparation conditions remain the same.
[0041] Comparative Example 4
[0042] The only difference between this comparative example and Example 2 is that copper tripeptide-1 was not added; all other components and preparation conditions remained the same.
[0043] The compound eye drops prepared in Examples 1-3 and Comparative Examples 1-4 were tested for physicochemical properties, including osmotic pressure and intrinsic viscosity, according to the General Chapters, Part IV of the Pharmacopoeia of the People's Republic of China (2020 Edition). A rheometer (TA, DHR-2) was used at 25°C with a shear rate starting from 0.1 s⁻¹. -1 ~100 s -1 Perform a peristaltic scan at 10 s. -1 The dynamic viscosity of the samples was recorded at the shear rate. The test results are shown in Table 1.
[0044] Table 1. Results of physicochemical property tests for compound eye drops.
[0045] As shown in Table 1, the osmotic pressure of the PDRN-containing compound eye drops prepared in Examples 1-3 of this invention is all within the range of 280-290 mOsm / L, close to the physiological isotonic conditions of tears (270-330 mOsm / L). This indicates that the non-ionic isotonic agent can effectively regulate the osmotic pressure, ensuring compatibility between the eye drops and the ocular surface environment, reducing irritation, and improving patient comfort. The intrinsic viscosity and dynamic viscosity of Examples 1-3 are also within the suitable range for ocular surface administration. This viscosity can effectively resist tear washout and prolong the residence time of the medication on the ocular surface, without causing difficulty in instillation or blurred vision due to excessive viscosity. This is due to the synergistic combination of the non-ionic thickener, sodium hyaluronate, and the non-ionic isotonic agent used in this invention, forming a gel network system with moderate viscosity and mucosal adhesion, laying the formulation foundation for solving the problem of "short residence time on the ocular surface".
[0046] The stability of the compound eye drops prepared in Examples 1-3 and Comparative Examples 2-4 was tested. The specific testing procedure was as follows: the compound eye drops prepared in Examples 1-3 and Comparative Examples 2-4 were placed in a stability chamber at 60℃, and samples were taken at 0, 5, 10, and 30 days. The average molecular weight of PDRN at each time point was determined using laser scattering-gel permeation chromatography (LLS-GPC). The test results are shown in Table 2.
[0047] Table 2. Stability test results of compound eye drops
[0048] As shown in Table 2, the PDRN-containing compound eye drops prepared in Examples 1-3 of this invention exhibited a PDRN degradation rate of 49.78-50.05% after 30 days in the accelerated stability test at 60℃. This indicates that the non-ionic system of this invention, combined with the mild preservative polyurethane biguanide and the preparation process of adjusting the pH before adding PDRN, can provide a stable microenvironment for PDRN, effectively inhibit its hydrolytic degradation, and significantly improve the stability of the formulation, thereby solving the problem of easy PDRN inactivation in the prior art.
[0049] Further analysis revealed that in Comparative Example 2, replacing polyaminopropyl biguanide with the traditional preservative benzalkonium chloride significantly increased the PDRN degradation rate from 50.05% to 64.55%, demonstrating that benzalkonium chloride has a significant destructive effect on nucleic acid macromolecules. In contrast, the polyaminopropyl biguanide used in this invention causes minimal damage to PDRN, making it an ideal preservative for PDRN formulations. Comparative Examples 3 and 4 showed PDRN degradation rates as high as 76.39% and 77.45%, respectively, far exceeding the 49.78% in Example 2. This result indicates that the amino acid mixture and the small molecule oligopeptide not only each fulfill their biological functions of providing metabolic substrates for collagen reconstruction and directly activating cell repair signaling pathways, but also jointly exert a chemical protective effect to stabilize PDRN: the chelating effect of the amino acid mixture reduces the catalytic degradation of PDRN by trace metal ions, and the thiol group of cysteine provides antioxidant protection; the small molecule oligopeptide can delay degradation by reducing PDRN adsorption at the container interface or forming a physical barrier. This further demonstrates that, in addition to synergistic effects on pharmacodynamics, the multiple components in the formulation of this invention also exhibit synergistic effects on formulation stability.
[0050] In summary, this invention addresses the technical challenge of PDRN's easy inactivation through a multi-dimensional synergistic approach, utilizing a non-ionic system design, the mild preservative properties of polyaminopropyl biguanide, and the stabilizing effects of an amino acid mixture and small molecule oligopeptides. This allows PDRN to maintain a degradation rate of approximately 50% within 30 days under accelerated conditions, significantly superior to comparative examples 2-4, thus providing a reliable formulation basis for achieving sustained ocular surface repair effects.
[0051] The corneal damage repair performance of the compound eye drops prepared in Examples 1-3 and Comparative Examples 1-4 was tested. The specific testing procedure was as follows: Thirty-five healthy New Zealand white rabbits, regardless of sex and weighing 1.8-2.5 kg, were randomly divided into 7 groups. Their corneas were irradiated with ultraviolet light (UV-B) for 10 minutes (750-800 μw / cm²). 2 Each group received 0.1 mL of the compound eye drops prepared in Examples 1-3 and Comparative Examples 1-4, respectively, applied to the right eye three times a day for five consecutive days. The left eye was not treated. The degree of corneal damage repair was assessed by measuring the release of lactate dehydrogenase (LDH) in the tear fluid. Increased LDH release indicated corneal damage, while decreased LDH release indicated corneal repair. LDH release was measured before irradiation, one day after irradiation, three days after irradiation, and five days after irradiation, and the average value was taken for each group. The LDH measurement method was as follows: 250 μL of physiological saline was applied topically to the eye and allowed to soak for 1 minute. Then, 50 μL of the sample was taken and the LDH release was measured using a fully automated biochemical analyzer (Hitachi 7600-020). The results are shown in Table 3.
[0052] Table 3. Results of corneal damage repair test using compound eye drops.
[0053] As shown in Table 3, after 5 days of administration in Examples 1-3, the LDH level in the right eye returned to normal (27-30 IU / L), while the level in Comparative Example 1 (PDRN deficiency) was as high as 118 IU / L, Comparative Example 2 (benzalkonium chloride replacing polyaminopropyl biguanide) was 92 IU / L, Comparative Example 3 (amino acid mixture deficiency) was 96 IU / L, and Comparative Example 4 (copper tripeptide-1 deficiency) was 92 IU / L. The LDH level in the right eye of each comparative example was significantly higher than that in the examples and was basically the same as that in the untreated left eye (87-92 IU / L), indicating that the corneal damage was not effectively repaired.
[0054] The above comparison demonstrates that this invention, through the quadruple synergy of PDRN, an amino acid mixture, small molecule oligopeptides, and nicotinamide, respectively activates the adenosine A2A pathway, provides substrates for collagen reconstruction metabolism, directly promotes corneal epithelial cell proliferation and migration, and provides anti-inflammatory energy, thus solving the problem of a single repair pathway from multiple targets. The combination of a non-ionic thickener and sodium hyaluronate achieves appropriate viscosity, effectively prolonging the ocular surface retention time and solving the problem of short ocular surface retention time. The non-ionic system design and the gentle preservative effect of polyaminopropyl biguanide protect PDRN activity, solving the problem of PDRN's easy inactivation. The absence or replacement of any key component leads to repair failure, confirming that the compound eye drops of this invention achieve a significant effect of complete corneal damage repair within 5 days through the synergistic effect of each component.
[0055] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A compound eye drop containing PDRN, characterized in that, The components include the following mass percentages: PDRN 0.05~1.0%, Sodium Hyaluronate 0.05~0.5%, Nicotinamide 0.05~1.0%, Amino Acid Mixture 0.01~0.5%, Small Molecule Oligopeptide 0.001~0.1%, Nonionic Thickener 0.1~1.0%, Nonionic Isotonic Agent 2.0~6.0%, Polyurethane Biguanide 0.0001~0.0015%, Balance: Water; The pH value of the compound eye drops containing PDRN is 6.5~7.
5.
2. The compound eye drops containing PDRN according to claim 1, characterized in that, The amino acid mixture is obtained by mixing glycine, proline, hydroxyproline, valine, leucine, lysine, serine, and cysteine.
3. The compound eye drops containing PDRN according to claim 2, characterized in that, The mass ratio of glycine, proline, hydroxyproline, valine, leucine, lysine, serine, and cysteine is 1:0.7~0.8:0.35~0.45:0.4~0.52:0.12~0.18:0.08~0.12:0.08~0.12:0.04~0.
08.
4. A compound eye drop containing PDRN according to any one of claims 1 to 3, characterized in that, The small molecule oligopeptides include one or more of palmitoyl tetrapeptide-7, acetyl hexapeptide-8, and copper tripeptide-1.
5. The compound eye drops containing PDRN according to claim 4, characterized in that, The nonionic thickener includes one or more of hydroxypropyl methylcellulose, hydroxypropyl ethylcellulose, polyvinylpyrrolidone, poloxamer 188, and poloxamer 407.
6. The compound eye drops containing PDRN according to claim 5, characterized in that, The nonionic isotonic agent includes one or more of glycerol, sorbitol, mannitol, and polyethylene glycol.
7. The compound eye drops containing PDRN according to claim 6, characterized in that, The compound eye drops containing PDRN also include a pH adjuster, which includes one or more of boric acid, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, and sodium dihydrogen phosphate.
8. A method for preparing a compound eye drop containing PDRN according to any one of claims 1 to 7, characterized in that, Includes the following steps: 1) Mix nonionic thickener, nonionic isotonic agent and some water, heat to dissolve, cool to room temperature, add sodium hyaluronate, nicotinamide and amino acid mixture, and then adjust the pH of the system to 6.5~7.5 to obtain pre-mixed solution; 2) Mix the pre-mixed solution, PDRN, small molecule oligopeptide, polyaminopropyl biguanide and the remaining water, and then adjust the pH of the system to 6.5~7.5 to obtain compound eye drops containing PDRN.
9. The method for preparing a compound eye drop containing PDRN according to claim 8, characterized in that, The heating and melting temperature described in step 1) is 70~80℃; The mass ratio of the water in step 1) to the remaining water in step 2) is 3~4:1~2; The mixing temperature in step 2) is 20~30℃.
10. The method for preparing a compound eye drop containing PDRN according to claim 9, characterized in that, The pH adjuster used in step 1) and the pH adjuster used in step 2) independently include one or more of boric acid, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, and sodium dihydrogen phosphate.