Meloxicam solution type ophthalmic preparation without bacteriostatic agent and tackifier and preparation method of meloxicam solution type ophthalmic preparation

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a meloxicam solution type ophthalmic preparation without a bacteriostatic agent and a tackifier as well as a preparation method and application of the meloxicam solution type ophthalmic preparation. The ophthalmic preparation is prepared from the following components in percentage by mass / volume: 0.05 to 0.5 percent of meloxicam or medicinal salt thereof, 1.0 to 10.0 percent of solubilizer, 0.067 to 2.0 percent of pH (Potential of Hydrogen) regulator, 0.1 to 2.0 percent of osmotic pressure regulator and water for injection, the solubilizing agent is one or two of hydroxypropyl beta-cyclodextrin and sulfobutyl beta-cyclodextrin, and the solubilizing agent is one or two of hydroxypropyl beta-cyclodextrin and sulfobutyl beta-cyclodextrin. The pH value of the ophthalmic preparation is 7.0-8.5, and the osmotic pressure molar concentration of the ophthalmic preparation is 250-450 mOsmol / kg. The ophthalmic preparation disclosed by the invention is not added with a bacteriostatic agent and a tackifier, has the advantages of better anti-inflammatory effect, no irritation, good compliance and safety, and easiness in industrial production of the preparation method, and can be used for treating eye inflammation.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical preparations, and more specifically, relates to a preparation method and application of a meloxicam ophthalmic preparation. Technical Background

[0002] At present, drugs for treating ocular inflammation mainly include corticosteroids, immunosuppressants, prostaglandin (PG) inhibitors and antihistamines. Among them, eye drops made of nonsteroidal anti-inflammatory drugs (NSAIDs) not only have strong permeability in the eye, but also have good anti-inflammatory effects, and avoid the side effects of long-term use of corticosteroids.

[0003] At present, it is believed that the mechanism of action of NSAIDs is mainly to inhibit prostaglandin cyclooxygenase (COX), preventing arachidonic acid from being converted into PG, thereby exerting anti-inflammatory, analgesic and antipyretic effects. COX has two isomers, namely COX-1 and COX-2. The stronger the inhibitory effect on COX-1, the greater the adverse reactions to the digestive tract, kidneys, etc.; and the stronger the inhibitory effect on COX-2, the more significant its anti-inflammatory and analgesic effects.

[0004] Meloxicam is a selective COX-2 inhibitor. The results of in vitro and in vivo experiments show that meloxicam has a strong inhibitory effect on COX-2 related to inflammation, while its inhibitory activity on COX-1, which is required to maintain normal physiology, is weak. Therefore, the side effects related to COX-1 are smaller. Therefore, using meloxicam, which selectively inhibits COX-2, as an ocular anti-inflammatory agent not only has good efficacy but also has little damage to ocular tissues, and has a good industrial development prospect.

[0005] Meloxicam is a poorly soluble drug, and cyclodextrin has the characteristics of high solubility and good inclusion effect on poorly soluble drug molecules. Therefore, it can be used to improve the solubility of poorly soluble drugs, enhance stability, reduce drug eye irritation, improve drug penetration into the cornea and bioavailability, and even produce a sustained release effect.

[0006] Meloxicam is added to a cyclodextrin aqueous solution, and the hydrophobic group is included in the hydrophobic cavity of the cyclodextrin to form a drug-cyclodextrin complex. The hydrophilic part of the cyclodextrin outside increases the solubility of the drug while preventing the drug from contacting with external factors, thereby increasing the stability of the drug. Currently, cyclodextrin inclusion compound preparations are sold in the Japanese and European markets. For example, Pfizer Pharmaceuticals Co., Ltd. has successfully developed an antipsychotic drug ziprasidone injection using SBE-β-CD as an inclusion material and has been launched in the United States.

[0007] Chinese patent application CN1301177A discloses a method for preparing meloxicam eye drops, specifically disclosing castor oil and Tween-80 as solvents and solubilizers, which makes the compliance and safety of eye medication a major concern. Chinese patent CN103110575B discloses a meloxicam eye drop preparation and a preparation method thereof, which can be used for the treatment of ocular inflammation and shows that meloxicam eye drops have excellent effects, but the prescription provided by the patent contains antibacterial agents such as ethyl hydroxybenzoate. In ophthalmic preparations for surgical operations and emergency treatment, it is not appropriate to add antibacterial agents or antioxidants or inappropriate additives, which will increase irritation and further aggravate inflammation. In addition, the prescription contains thickeners such as povidone and hydroxypropyl methylcellulose, which increase their retention time in the eye, further deepen irritation and aggravate inflammation. The above problems all lead to the existence of major safety hazards in the use of the eye drop preparation, and poor patient compliance.

[0008] Therefore, based on the above-mentioned defects in the prior art, developing a meloxicam eye drop that does not contain antibacterial agents but can achieve sterility assurance, and can effectively accelerate the healing of eye wounds and alleviate inflammatory symptoms, and reduce eye irritation, is still a key technical problem that needs to be solved urgently. Summary of the invention

[0009] The purpose of the present invention is to solve the shortcomings of the above technical background and develop a meloxicam solution-type ophthalmic preparation without antibacterial agent and viscosity enhancer, and a preparation method and use thereof.

[0010] To achieve the above object, the technical solution adopted by the present invention is:

[0011] In the first aspect, the present invention provides a meloxicam solution-type ophthalmic preparation that does not contain an antibacterial agent and a viscosity enhancer. The ophthalmic preparation is composed of the following components, measured by mass volume percentage: 0.05% to 0.5% of meloxicam or a pharmaceutically acceptable salt thereof, 1.0 to 10.0% of a solubilizer, 0.067 to 2.0% of a pH regulator, 0.1 to 2.0% of an osmotic pressure regulator, and 84.5% to 99% of water for injection, and the sum of the percentages of the various components is 100%.

[0012] As an optional manner, in the above-mentioned ophthalmic preparation, the ophthalmic preparation is composed of the following components, measured by mass volume percentage: 0.05% to 0.2% of meloxicam or a pharmaceutically acceptable salt thereof, 1.0 to 5.0% of a solubilizer, 0.067 to 2.0% of a pH adjuster, 0.1 to 1.5% of an osmotic pressure regulator, and an appropriate amount of water for injection, and the sum of the percentages of each component is 100%.

[0013] As an optional mode, in the above ophthalmic preparation, the pharmaceutically acceptable salt of meloxicam is diethylamine salt, methylglucamine salt, sodium salt, potassium salt or ammonium salt.

[0014] Preferably, the pharmaceutically acceptable salt of meloxicam is diethylamine salt.

[0015] As an optional mode, in the above ophthalmic preparation, the solubilizer is one or both of hydroxypropyl-beta-cyclodextrin and sulfobutyl-beta-cyclodextrin.

[0016] As an optional mode, in the above ophthalmic preparation, the solubilizer is hydroxypropyl-beta-cyclodextrin, and preferably the hydroxypropoxy content thereof is 16% to 45%.

[0017] As an optional mode, in the above-mentioned ophthalmic preparation, the pH adjuster is one or more of sodium hydroxide, hydrochloric acid, boric acid, borax, sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, citric acid, sodium citrate, aminocaproic acid, and tromethamine.

[0018] As an alternative, in the above ophthalmic preparation, the preferred pH range is 7.0 to 8.5.

[0019] As an optional mode, in the above-mentioned ophthalmic preparation, the osmotic pressure regulator is one or more of sodium chloride, potassium chloride, boric acid, borax, sodium sulfate, potassium sulfate, potassium nitrate, sodium nitrate, mannitol, glycerol, propylene glycol, and glucose.

[0020] As an optional mode, in the above ophthalmic preparation, a horizontal flow pump is used in the solution preparation process of the ophthalmic preparation preparation method.

[0021] As an optional mode, in the above-mentioned ophthalmic preparation, during the solution preparation process of the ophthalmic preparation preparation method, the pH adjuster is added first and then meloxicam is added.

[0022] As an optional manner, in the above-mentioned ophthalmic preparation, the inner packaging material of the ophthalmic preparation is a low-density polyethylene bacteria-barrier multi-dose medicinal eye drop bottle or a low-density polyethylene single-dose medicinal eye drop bottle.

[0023] In the second aspect, the present invention provides a method for preparing the meloxicam solution-type ophthalmic preparation free of an antibacterial agent and a viscosity enhancer as described in the first aspect above, the preparation method comprising the following steps: dissolving a solubilizing agent in a certain amount of water to prepare solution 1; dissolving a pH adjuster and meloxicam in a certain amount of water in that order to prepare solution 2; mixing solution 1 with solution 2, adding other excipients in sequence, stirring until completely dissolved, adjusting the pH, adding water for injection to the full amount, and filtering with a microporous membrane to obtain the product.

[0024] As an optional manner, the preparation method comprises the following steps: dissolving a solubilizing agent in a certain amount of water to prepare solution 1; dissolving a pH adjuster and meloxicam in a certain amount of water in sequence to prepare solution 2; using a horizontal flow pump to mix solution 1 and solution 2 through a mixer, adding other auxiliary materials in sequence, stirring until completely dissolved, adjusting the pH, adding water for injection to the full amount, and filtering with a microporous membrane to obtain the product.

[0025] In the third aspect, the present invention provides the use of the meloxicam solution-type ophthalmic preparation containing no antibacterial agent and no viscosity enhancer as described in the first aspect above, or the meloxicam solution-type ophthalmic preparation containing no antibacterial agent and no viscosity enhancer prepared by the preparation method described in the second aspect above, in the preparation of a drug for preventing or treating non-infectious ophthalmic inflammation.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] (1) The antibacterial agent and the viscosity enhancer are removed from the ophthalmic preparation of the present invention, and a horizontal flow pump is used during the solution preparation process to increase the encapsulation rate and improve the solution stability.

[0028] (2) The present invention investigated the stability of eye drops prepared with different orders of adding excipients and found that the stability was better when the pH adjuster was added first and then meloxicam.

[0029] (3) The present invention unexpectedly discovered that after the antibacterial agent and the viscosity increasing agent are removed, the eye irritation is reduced, the healing of eye wounds and the disappearance of inflammatory symptoms are accelerated, and the eye compliance is improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a diagram of the ocular efficacy of meloxicam eye drops.

[0031] Figure 2 This is a diagram of eye irritation after continuous administration of meloxicam eye drops. DETAILED DESCRIPTION

[0032] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0033] If no specific techniques or conditions are specified in the examples, the techniques or conditions described in the literature in the field or the product instructions are used. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0034] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0035] Unless otherwise indicated, the percentages used in the prescriptions of the present invention are all percentages by mass and volume, with the unit of mass being g and the unit of volume being mL.

[0036] Preparation Example Part:

[0037] Embodiment 1:

[0038] prescription:

[0039] name Prescription amount (g) Meloxicam 0.1 Hydroxypropyl Beta-Cyclodextrin 3.3 Sodium hydroxide 0.067 Boric acid 1 Sodium chloride 0.34 water Add to 100mL

[0040] Preparation method: Weigh the prescribed amount of hydroxypropyl beta-cyclodextrin (hydroxypropoxy content 30%), add it to 33g of water for injection, stir until dissolved, add the prescribed amount of meloxicam and continue stirring for 10 minutes, then add the prescribed amount of sodium hydroxide and continue stirring for 15 minutes. Weigh the prescribed amount of boric acid and sodium chloride, add them to the above solution in sequence, add water for injection to 90g, adjust the pH to 7.7, add water for injection to the full amount, stir well, and filter with a 0.22μm microporous membrane to obtain the product.

[0041] Example 2: Different order of adding auxiliary materials

[0042] prescription:

[0043] name Prescription amount (g) Meloxicam 0.1 Hydroxypropyl Beta-Cyclodextrin 3.3 Sodium hydroxide 0.067 Boric acid 1 Sodium chloride 0.34 water Add to 100mL

[0044] Preparation method: Weigh the prescribed amount of hydroxypropyl beta-cyclodextrin (hydroxypropoxy content 30%) and sodium hydroxide, add to 33g of water for injection, stir until dissolved, add the prescribed amount of meloxicam and continue stirring for 15 minutes. Weigh the prescribed amount of boric acid and sodium chloride, add to the above solution in sequence, add water for injection to 90g, adjust the pH to 7.7, add water for injection to the full amount, stir well, and filter with a 0.22μm microporous membrane to obtain.

[0045] Example 3: Horizontal flow pump mixing process

[0046] prescription:

[0047] name Prescription amount (g) Meloxicam 0.1 Hydroxypropyl Beta-Cyclodextrin 3.3 Sodium hydroxide 0.067 Boric acid 1 Sodium chloride 0.34 water Add to 100mL

[0048] Preparation method: Weigh the prescribed amount of hydroxypropyl beta-cyclodextrin (hydroxypropoxy content 30%), add it to 33g of water for injection, stir until dissolved, and obtain solution 1; weigh the prescribed amount of sodium hydroxide, add it to 33g of water for injection, weigh the prescribed amount of meloxicam and add it thereto, continue stirring to dissolve, and obtain solution 2; use a horizontal flow pump to mix solution 1 and solution 2 at the same flow rate through a mixer, weigh the prescribed amount of boric acid and sodium chloride, add them to the above mixed solution in turn, add water for injection to 90g, adjust the pH to 7.7, add water for injection to the full amount, stir well, and filter with a 0.22μm microporous filter membrane to obtain.

[0049] Example 4: Horizontal flow pump mixing process, hydroxypropyl beta-cyclodextrin hydroxypropoxy content 16%

[0050] prescription:

[0051] name Prescription amount (g) Meloxicam 0.1 Hydroxypropyl Beta-Cyclodextrin 3.3 Sodium hydroxide 0.067 Boric acid 1 Sodium chloride 0.34 water Add to 100mL

[0052] Preparation method: Weigh the prescribed amount of hydroxypropyl beta-cyclodextrin (hydroxypropoxy content 16%), add it to 33g of water for injection, stir until dissolved, and obtain solution 1; weigh the prescribed amount of sodium hydroxide, add it to 33g of water for injection, weigh the prescribed amount of meloxicam and add it thereto, continue stirring to dissolve, and obtain solution 2; use a horizontal flow pump to mix solution 1 and solution 2 at the same flow rate through a mixer, weigh the prescribed amount of boric acid and sodium chloride, add them to the above mixed solution in turn, add water for injection to 90g, adjust the pH to 7.7, add water for injection to the full amount, stir well, and filter with a 0.22μm microporous filter membrane to obtain.

[0053] Example 5: Horizontal flow pump mixing process, hydroxypropyl beta-cyclodextrin hydroxypropoxy content 45%

[0054] prescription:

[0055] name Prescription amount (g) Meloxicam 0.1 Hydroxypropyl Beta-Cyclodextrin 3.3 Sodium hydroxide 0.067 Boric acid 1 Sodium chloride 0.34 water Add to 100mL

[0056] Preparation method: Weigh the prescribed amount of hydroxypropyl beta-cyclodextrin (hydroxypropoxy content 45%), add it to 33g of water for injection, stir until dissolved, and obtain solution 1; weigh the prescribed amount of sodium hydroxide, add it to 33g of water for injection, weigh the prescribed amount of meloxicam and add it thereto, continue stirring to dissolve, and obtain solution 2; use a horizontal flow pump to mix solution 1 and solution 2 at the same flow rate through a mixer, weigh the prescribed amount of boric acid and sodium chloride, add them to the above mixed solution in turn, add water for injection to 90g, adjust the pH to 7.7, add water for injection to the full amount, stir well, and filter with a 0.22μm microporous filter membrane to obtain.

[0057] Comparative Example 1:

[0058] prescription:

[0059] name Prescription amount (g) Meloxicam diethylamine salt (calculated as meloxicam) 0.1 Hydroxypropyl Beta-Cyclodextrin 1 Hydroxypropyl methylcellulose 1 Borax 3.0 Boric acid 1.2 Ethylparaben 0.03 Sodium chloride 0.43 water Add to 100mL

[0060] Preparation method: Weigh the prescribed amount of hydroxypropyl beta-cyclodextrin and dissolve it in 90 mL of water for injection, add borax and boric acid to dissolve, heat in a water bath to 80°C, add 1.0 g of meloxicam, stir, add other excipients in sequence after complete dissolution, continue stirring until complete dissolution, adjust the pH to 8.0, add water for injection to 100 mL, filter with a 0.22 μm microporous membrane, and obtain. Effect Example Part:

[0061] Effect Example 1: Stability test method of eye drops prepared in each example and comparative example 1. Influencing factor test

[0062] The eye drops prepared by each prescription process were placed at 60°C for 10 days. The results are shown in Table 1 below.

[0063]

[0064]

[0065] From the stability results of Examples 1-5 and Comparative Example 1, it can be seen that:

[0066] (1) Adjusting the order of adding excipients and adding sodium hydroxide before adding meloxicam can improve the stability of eye drops.

[0067] (2) The use of a horizontal flow pump process can improve the stability of eye drops.

[0068] (3) The hydroxypropoxy content of hydroxypropyl-beta-cyclodextrin affects the stability of eye drops. The higher the hydroxypropoxy content, the better the stability of the eye drops.

[0069] (4) Under the process conditions of the present invention, the eye drops without adding hypromellose have better stability than those with adding this ingredient.

[0070] Effect Example 2: Pharmacodynamic Evaluation

[0071] The pharmacodynamics of the eye drops of each embodiment and comparative example were evaluated by using the rabbit anterior chamber puncture test and the capsicum tincture-induced eye inflammation test. The results showed that the meloxicam eye drops prepared by the prescription process of the present invention had better anti-inflammatory effect than the comparative example. The specific test process and results are as follows:

[0072] 1. Rabbit anterior chamber puncture test

[0073] Twenty-four rabbits without eye abnormalities were randomly divided into four groups, each with six rabbits, namely, negative control group, Example 3 group, Example 5 group, and Comparative Example 1 group. 0.05 mL of the drug solution was instilled into the experimental eyes of the rabbits in each group, and the eyes were passively closed for 10 seconds. After 45 minutes, 0.2 mL of 1% tetracaine was dropped under local anesthesia, and 4 1 / 2The corneal limbus was punctured with a needle of injection number 2 to obtain 0.2 mL of aqueous humor. After 90 minutes, the aqueous humor was punctured again to obtain a second batch of aqueous humor. The two batches of aqueous humor were diluted 2 times and 50 times respectively. Then, 0.05 mL of distilled water, aqueous humor diluent and standard protein solution were taken, and 3 mL of Coomassie brilliant blue staining solution were added respectively. After reacting for 10 minutes, the absorbance was measured at 595 nm, and the protein content was calculated according to the following formula:

[0074]

[0075] The results showed that Example 3 and Example 5 were more effective than Comparative Example 1 in inhibiting the increase in aqueous humor protein concentration caused by anterior chamber puncture, with significant differences. The specific test results are shown in Table 3 below.

[0076] Table 3 Meloxicam eye drops anterior chamber puncture test aqueous humor protein concentration results (mean ± SD, n = 6)

[0077]

[0078] Note: Compared with control group 1, **P < 0.01; ***P < 0.001; compared with negative control group, △ P < 0.05; △△ P < 0.01; △△△ P<0.001.

[0079] 2. Test on eye inflammation caused by pepper tincture

[0080] 18 rabbits with no eye abnormalities were randomly divided into 3 groups, 6 rabbits in each group, namely the negative control group, the 0.1% meloxicam control group (Comparative Example 1) and the 0.1% meloxicam treatment group (Example 3). Before administration, 0.1 mL of 5% capsicum tincture was dripped into the experimental eye (left) of each rabbit, and the eye was passively closed for about 10 seconds to cause an inflammatory reaction in the eye, which was manifested as congestion, edema and increased secretions of the iris, conjunctiva and cornea. Administration began 30 minutes later, with 0.1 mL of the drug solution dripped into each group each time, once every 30 minutes, for a total of 6 times, and then once every 1 hour, for a total of 5 times, and observed regularly. Score and record according to the eye irritation reaction scoring standard (Table 4) below. Calculate the mean of the total score of the experimental eyes in different experimental groups. The results are shown in Table 5 Eye irritation reaction score. Eye efficacy diagram is shown in Figure 1 .

[0081] Table 4 Eye irritation response score standard

[0082]

[0083]

[0084] Table 5 Inhibitory effect of meloxicam eye drops on rabbit ocular inflammation induced by pepper tincture (mean ± SD, n = 6)

[0085]

[0086] Note: Compared with the comparative example 1, * P < 0.05; ** P < 0.01; *** P<0.001; compared with the negative control group, Δ P < 0.05; ΔΔ P < 0.01; ΔΔΔ P<0.001.

[0087] Compared with the negative control group, the 0.1% meloxicam treatment group (Example 3) has significantly controlled inflammation since 1 hour, and the 0.1% meloxicam control group (Comparative Example 1) has significantly controlled inflammation since 4 hours, indicating that Example 3 can take effect earlier to control inflammation. From 1 hour to 8 hours, the eye scores of the 0.1% meloxicam treatment group (Example 3) and the 0.1% meloxicam group (Comparative Example 1) are significantly different. And as time goes by, the anti-inflammatory effect becomes more obvious.

[0088] 3. Comparison of eye irritation of meloxicam eye drops

[0089] 24 rabbits were randomly divided into 4 groups, namely, a blank group (NaCl), a negative control group (blank eye drops without active ingredients), a 0.1% meloxicam eye drops test group (Example 3), and a 0.1% meloxicam eye drops control group (Comparative Example 1). The left eye of each group of rabbits was administered 4 times a day, 100 μL each time, for 21 consecutive days. One hour after the last administration, the left eye of the rabbit was evaluated for in vivo irritation using the improved Draize test method, including corneal transparency, iris redness, conjunctival congestion, swelling and secretions to evaluate the degree of eye irritation damage. The evaluation criteria are shown in Table 6, the scoring results are shown in Table 7, and the irritation diagram is shown in Table 6. Figure 2 .

[0090] Table 6 Eye irritation evaluation criteria

[0091] Points evaluate 0～3 Non-irritating 4～8 Mild irritant 9～12 Moderate irritation 13～16 Severe irritation

[0092] The total score of 0-3 represents no irritation, 4-8 represents mild irritation, 9-12 represents moderate irritation, and 13-16 represents strong irritation. The results are shown in Table 7.

[0093] Table 7 Ocular irritation scoring results of meloxicam eye drops (mean ± SD, n = 6)

[0094]

[0095] Note: Compared with the comparative example 1, *** P<0.001; compared with the negative control group, ΔΔΔ P<0.001.

[0096] Table 7 shows that the negative control group (blank excipient) is mildly irritating. Compared with the blank group, the integrity of the cornea is damaged, the iris is wrinkled or the color is darkened, and the conjunctiva is congested, swollen, and the secretions increase. Figure 2 It can be seen that long-term use of eye drops containing antibacterial agents and viscosity enhancers (such as benzalkonium chloride and hydroxypropyl methylcellulose) (Comparative Example 1) has a destructive effect on the integrity of the cornea, and causes redness and swelling of the conjunctiva and increased secretions.

[0097] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A meloxicam solution-type ophthalmic preparation free of antibacterial agents and viscosity enhancers, characterized in that: The ophthalmic preparation is composed of the following components in terms of mass volume percentage: 0.05% to 0.5% of meloxicam or its pharmaceutically acceptable salt, 1.0 to 10.0% of a solubilizer, 0.067 to 2.0% of a pH regulator, 0.1 to 2.0% of an osmotic pressure regulator, and an appropriate amount of water for injection, and the sum of the percentages of the various components is 100%.

2. The meloxicam solution-type ophthalmic preparation containing no antibacterial agent and no viscosity increasing agent according to claim 1, characterized in that: The pharmaceutically acceptable salt of meloxicam is diethylamine salt, methylglucamine salt, sodium salt, potassium salt or ammonium salt, preferably diethylamine salt.

3. The meloxicam solution-type ophthalmic preparation containing no antibacterial agent and no viscosity increasing agent according to claim 1, characterized in that: The solubilizing agent is one or both of hydroxypropyl beta-cyclodextrin and sulfobutyl beta-cyclodextrin.

4. The meloxicam solution-type ophthalmic preparation containing no antibacterial agent and no viscosity increasing agent according to claim 3, characterized in that: The solubilizer is hydroxypropyl beta-cyclodextrin, and preferably the hydroxypropoxy content thereof is 16% to 45%.

5. The meloxicam solution-type ophthalmic preparation containing no antibacterial agent and no viscosity increasing agent according to claim 1, characterized in that: The pH regulator is one or more of sodium hydroxide, hydrochloric acid, boric acid, borax, sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, citric acid, sodium citrate, aminocaproic acid, and tromethamine, and the preferred pH range is 7.0 to 8.5; the osmotic pressure regulator is one or more of sodium chloride, potassium chloride, boric acid, borax, sodium sulfate, potassium sulfate, potassium nitrate, sodium nitrate, mannitol, glycerol, propylene glycol, and glucose.

6. The meloxicam solution-type ophthalmic preparation containing no antibacterial agent and no viscosity increasing agent according to claim 1, characterized in that: During the solution preparation process of the ophthalmic preparation preparation method, the pH adjuster is added first and then meloxicam is added.

7. The meloxicam solution-type ophthalmic preparation containing no antibacterial agent and no viscosity increasing agent according to claim 1, characterized in that: The inner packaging material of the ophthalmic preparation is a low-density polyethylene bacteria-blocking multi-dose medicinal eye drop bottle or a low-density polyethylene single-dose medicinal eye drop bottle.

8. The method for preparing the meloxicam solution-type ophthalmic preparation free of antibacterial agent and viscosity increasing agent according to any one of claims 1 to 7, characterized in that: The preparation method comprises the following steps: dissolving a solubilizing agent in a certain amount of water to prepare solution 1; dissolving a pH adjusting agent and meloxicam in a certain amount of water in sequence to prepare solution 2; mixing solution 1 with solution 2, adding other auxiliary materials in sequence, stirring until completely dissolved, adjusting the pH, adding water for injection to the full amount, filtering with a microporous filter membrane, and obtaining the product.

9. Use of the meloxicam solution ophthalmic preparation containing no antibacterial agent and no viscosity enhancer according to any one of claims 1 to 7 or the meloxicam solution ophthalmic preparation containing no antibacterial agent and no viscosity enhancer prepared by the preparation method according to claim 8 in the preparation of a medicament for preventing or treating non-infectious ophthalmic inflammation.

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