CN114306228A - Diquafosol sodium eye drops and preparation method thereof - Google Patents
Diquafosol sodium eye drops and preparation method thereof Download PDFInfo
- Publication number
- CN114306228A CN114306228A CN202210071074.9A CN202210071074A CN114306228A CN 114306228 A CN114306228 A CN 114306228A CN 202210071074 A CN202210071074 A CN 202210071074A CN 114306228 A CN114306228 A CN 114306228A
- Authority
- CN
- China
- Prior art keywords
- sodium
- diquafosol
- solution
- eye drops
- boric acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention belongs to an ophthalmic preparation, and provides diquafosol sodium eye drops and a preparation method thereof. In the diquafosol sodium eye drops provided by the invention, boric acid and edetate disodium are used together, so that the antibacterial performance of boric acid can be enhanced, the antibacterial effect of the diquafosol sodium eye drops is ensured, the toxic antibacterial agent benzalkonium chloride is prevented from being used in the product, and the harm to a human body is reduced. The disodium edetate and boric acid have the antiseptic property, so that the diquafosol sodium eye drops have excellent antiseptic property; meanwhile, disodium edetate can improve the oxidation resistance of the sodium diquafosol eye drops, thereby improving the stability of sodium diquafosol. The boric acid and the sodium hydroxide form a buffer pair, and the pH of the diquafosol sodium eye drops is stabilized. Potassium chloride and boric acid are adopted to replace part of sodium chloride, the osmotic pressure of the diquafosol sodium eye drops is adjusted, the sodium ion content in the diquafosol sodium eye drops is reduced, and the low-sodium effect is achieved.
Description
Technical Field
The invention relates to the technical field of ophthalmic preparations, in particular to diquafosol sodium eye drops and a preparation method thereof.
Background
The diquafosol sodium eye drops are suitable for dry eye patients diagnosed with keratoconjunctival epithelial damage accompanied with lacrimal disorders. The ophthalmic preparation is packaged in multiple doses and is repeatedly used for multiple times. Once the ophthalmic preparation is unsealed, the ophthalmic preparation is easily polluted by tears and microorganisms in the air in the using and storing processes, thereby generating potential safety hazards. In order to prevent the ophthalmic preparation from being secondarily polluted by microorganisms in the process of repeatedly using the ophthalmic preparation after being unsealed, bacteriostatic agents (preservative) are added into the ophthalmic preparation. Bacteriostatic agents were used in almost all eye drop formulations in the "Chinese Hospital's Specification for preparation". Bacteriostatic agents, also known as preservatives or preservatives, are chemicals that inhibit the growth and reproduction of pathogenic microorganisms, and their primary application in pharmaceutical practice is to prevent microbial contamination of drugs.
Although bacteriostatic agents have a certain positive significance in preventing microbial contamination, adverse reactions of bacteriostatic agents are gradually recognized by people. Liu 'ei ming et al (Liu' ei ming, Li Wei, Wang Ben Min, damage to ocular surface of bacteriostatic agent in ophthalmic preparation, China Hospital pharmaceutical journal 2002, 22(6), 371 one 373) reported that the presence of bacteriostatic agent can cause irritation to surface cells of eyes. The bacteriostatic agent component in the ophthalmic preparation can directly influence the component of tears, change the microenvironment on the surface of eyeballs, and lead epithelial cells which are originally closely connected to be loosened and damaged, and severe patients have corneal epithelial shedding, defect and epithelial erosion and can generate corneal ulcer which can dissolve, perforate and lose sight of the cornea. Ningli et al (Ningli, China journal of Hospital pharmacy 2007, 42(23), 1836 and 1838, which pay attention to the reasonable use and quality control of bacteriostatic agents in the development process of ophthalmic preparations, refer to the problem caused by the abuse of bacteriostatic agents, and especially have higher potential risk for ophthalmic preparations which need to be frequently used.
Currently, benzalkonium chloride is a commonly used bacteriostatic agent in ophthalmic preparations, but bacteriostatic agents such as benzalkonium chloride can damage tear film and damage ocular surface epithelial cells, the damage is aggravated along with the prolonging of the administration time, and for patients suffering from glaucoma, xerophthalmia and the like which need to be administered for a long time, the use of the bacteriostatic agent-containing eye drops can cause secondary damage to the ocular tissues of the patients. In order to ameliorate the side effects of ophthalmic formulations containing benzalkonium chloride, researchers have replaced benzalkonium chloride with non-toxic, but bacteriostatic substances. For example: chinese patent with publication number CN 108853016A discloses diquafosol sodium eye drops, each 1mL of which contains the following components in percentage by weight/volume: 30% of diquafosol sodium (calculated as anhydrous substance), 3% -6% of chitosan, 8% -12% of boric acid, 2% -4% of borax and 1mL of purified water. Although benzalkonium chloride with high toxicity is not used in the diquafosol sodium eye drops, boric acid and borax which are antibacterial substances are added in large quantities, and the potential risk still exists.
Disclosure of Invention
In view of the above, the present invention aims to provide diquafosol sodium eye drops and a preparation method thereof, wherein the diquafosol sodium eye drops provided by the present invention have a small boric acid dosage and a small potential risk.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides diquafosol sodium eye drops which comprise the following components: diquafosol sodium, edetate disodium, disodium hydrogen phosphate, sodium chloride, potassium chloride, boric acid, a pH regulator and water;
the mass concentration of the sodium diquafosol is 3%;
the mass concentration of the edetate disodium is 0.005-0.015%;
the mass concentration of the disodium hydrogen phosphate is 0.2-0.4%;
the mass concentration of the sodium chloride is 0.3-0.5%;
the mass concentration of the potassium chloride is 0.15-0.2%;
the mass concentration of the boric acid is 2-4%;
the pH adjuster includes sodium hydroxide.
Preferably, the pH value of the diquafosol sodium eye drops is 7.5-8.5.
Preferably, the mole concentration ratio of the diquafosol sodium eye drops in osmotic pressure is 1.0-1.1.
Preferably, the water comprises water for injection.
The preparation method of the diquafosol sodium eye drops comprises the following steps:
dissolving edetate disodium in water to obtain edetate disodium solution;
dissolving sodium chloride and potassium chloride in water to obtain a sodium chloride-potassium chloride solution;
mixing the edetate disodium solution and a sodium chloride-potassium chloride solution to obtain a first solution;
dissolving disodium hydrogen phosphate and boric acid in water to obtain a disodium hydrogen phosphate-boric acid solution;
mixing the first solution, a disodium hydrogen phosphate-boric acid solution and sodium diquafosol to obtain a second solution;
and mixing the second solution and a pH regulating agent to obtain the diquafosol sodium eye drops.
The invention provides diquafosol sodium eye drops which comprise the following components: diquafosol sodium, edetate disodium, disodium hydrogen phosphate, sodium chloride, potassium chloride, boric acid, a pH regulator and water; the mass concentration of the sodium diquafosol is 3%; the mass concentration of the edetate disodium is 0.005-0.015%; the mass concentration of the disodium hydrogen phosphate is 0.2-0.4%; the mass concentration of the sodium chloride is 0.3-0.5%; the mass concentration of the potassium chloride is 0.15-0.2%; the mass concentration of the boric acid is 2-4%; the pH adjuster includes sodium hydroxide. In the diquafosol sodium eye drops provided by the invention, boric acid and edetate disodium are used together, so that the antibacterial performance of boric acid can be enhanced, the antibacterial effect of the diquafosol sodium eye drops is ensured, the toxic antibacterial agent benzalkonium chloride is prevented from being used in the product, and the harm to a human body is reduced. The disodium edetate and boric acid have the antiseptic property, so that the diquafosol sodium eye drops have excellent antiseptic property; meanwhile, disodium edetate can improve the oxidation resistance of the diquafosol sodium eye drops, so that the stability of the diquafosol sodium eye drops is improved. The boric acid and the sodium hydroxide form a buffer pair, and the pH of the diquafosol sodium eye drops is stabilized. Potassium chloride and boric acid are adopted to replace part of sodium chloride, the osmotic pressure of the diquafosol sodium eye drops is adjusted, the sodium ion content in the diquafosol sodium eye drops is reduced, and the low-sodium effect is achieved.
The invention also provides a preparation method of the diquafosol sodium eye drops, which comprises the following steps: dissolving edetate disodium in water to obtain edetate disodium solution; dissolving sodium chloride and potassium chloride in water to obtain a sodium chloride-potassium chloride solution; mixing the edetate disodium solution and a sodium chloride-potassium chloride solution to obtain a first solution; dissolving disodium hydrogen phosphate and boric acid in water to obtain a disodium hydrogen phosphate-boric acid solution; mixing the first solution, a disodium hydrogen phosphate-boric acid solution and sodium diquafosol to obtain a second solution; and mixing the second solution and a pH regulating agent to obtain the diquafosol sodium eye drops. The preparation method provided by the invention is simple to operate and easy to industrialize.
Detailed Description
The invention provides diquafosol sodium eye drops which comprise the following components: diquafosol sodium, edetate disodium, disodium hydrogen phosphate, sodium chloride, potassium chloride, boric acid, a pH regulator and water;
the mass concentration of the sodium diquafosol is 3%;
the mass concentration of the edetate disodium is 0.005-0.015%;
the mass concentration of the disodium hydrogen phosphate is 0.2-0.4%;
the mass concentration of the sodium chloride is 0.3-0.5%;
the mass concentration of the potassium chloride is 0.15-0.2%;
the mass concentration of the boric acid is 2-4%;
the pH adjuster includes sodium hydroxide.
In the present invention, the starting materials used in the present invention are preferably commercially available products unless otherwise specified.
The diquafosol sodium eye drops comprise diquafosol sodium, wherein the mass concentration of the diquafosol sodium is 3%. In the present invention, the mass concentration refers to the mass of solute in g per 100mL of diquafosol sodium eye drops.
The diquafosol sodium eye drops comprise disodium edetate, wherein the mass concentration of the disodium edetate is 0.005-0.015%, more preferably 0.007-0.013%, more preferably 0.009-0.011%, and particularly preferably 0.005%, 0.01% or 0.015%.
The diquafosol sodium eye drops comprise disodium hydrogen phosphate, wherein the mass concentration of the disodium hydrogen phosphate is 0.2-0.4%, preferably 0.25-0.35%, and more preferably 0.3%.
The diquafosol sodium eye drops comprise sodium chloride, wherein the mass concentration of the sodium chloride is 0.3-0.5%, preferably 0.35-0.45%, and more preferably 0.4%.
The diquafosol sodium eye drops comprise potassium chloride, wherein the mass concentration of the potassium chloride is 0.15-0.2%, preferably 0.16-0.19%, and more preferably 0.17-0.18%.
The diquafosol sodium eye drops comprise boric acid, wherein the mass concentration of the boric acid is 2-4%, preferably 2.5-3.5%, and more preferably 3%.
The diquafosol sodium eye drops provided by the invention comprise a pH regulator, wherein the pH regulator comprises sodium hydroxide. In the present invention, the sodium hydroxide is preferably used in the form of an aqueous sodium hydroxide solution, and the concentration of the aqueous sodium hydroxide solution is preferably 0.1 mol/L. The dosage of the sodium hydroxide aqueous solution is not particularly limited, as long as the pH of the diquafosol sodium eye drops is 7.5-8.5.
The diquafosol sodium eye drop provided by the invention comprises water. In the present invention, the water preferably includes water for injection.
In the invention, the pH value of the diquafosol sodium eye drops is preferably 7.5-8.5, more preferably 7.7-8.3, and even more preferably 7.9-8.1.
In the invention, the osmotic pressure molar concentration ratio of the diquafosol sodium eye drops is preferably 1.0-1.1.
The invention also provides a preparation method of the diquafosol sodium eye drops, which comprises the following steps:
dissolving edetate disodium in water to obtain edetate disodium solution;
dissolving sodium chloride and potassium chloride in water to obtain a sodium chloride-potassium chloride solution;
mixing the edetate disodium solution and a sodium chloride-potassium chloride solution to obtain a first solution;
dissolving disodium hydrogen phosphate and boric acid in water to obtain a disodium hydrogen phosphate-boric acid solution;
mixing the first solution, a disodium hydrogen phosphate-boric acid solution and sodium diquafosol to obtain a second solution;
and mixing the second solution and a pH regulating agent to obtain the diquafosol sodium eye drops.
The edetate disodium is dissolved by water to obtain an edetate disodium solution. In the present invention, the dissolution of edetate disodium in water is preferably carried out under stirring.
The invention dissolves sodium chloride and potassium chloride with water to obtain sodium chloride-potassium chloride solution. In the present invention, the dissolution of the sodium chloride and potassium chloride with water is preferably carried out under stirring.
After obtaining the edetate disodium solution and the sodium chloride-potassium chloride solution, the invention mixes the edetate disodium solution and the sodium chloride-potassium chloride solution to obtain a first solution. In the present invention, the mixing of the edetate disodium solution and the sodium chloride-potassium chloride solution is preferably performed under stirring.
The disodium hydrogen phosphate and boric acid are dissolved by water to obtain a disodium hydrogen phosphate-boric acid solution. In the present invention, the dissolution of the disodium hydrogen phosphate and boric acid with water is preferably performed under stirring.
After the first solution and the disodium hydrogen phosphate-boric acid solution are obtained, the invention mixes the first solution, the disodium hydrogen phosphate-boric acid solution and the diquafosol sodium to obtain a second solution. In the present invention, the first solution, the disodium hydrogen phosphate-boric acid solution, and the sodium diquafosol are preferably mixed under stirring.
After the second solution is obtained, the second solution and the pH regulating agent are mixed to obtain the diquafosol sodium eye drops. In the present invention, the mixing of the second solution and the pH adjusting agent is preferably performed under stirring.
After the mixing, preferably, the constant volume is also included; the volume of the water added in constant volume is preferably less than or equal to 9 percent of the volume of the water of the diquafosol sodium eye drops.
In the invention, after the constant volume is performed, the method preferably further comprises filling; the filling is preferably carried out under aseptic conditions.
The diquafosol sodium eye drops and the preparation method thereof provided by the present invention will be described in detail with reference to the following examples, but they should not be construed as limiting the scope of the present invention.
Example 1
Adding 0.005g of edetate disodium into 70mL of injection water at 30-35 ℃, and stirring to obtain an edetate disodium solution.
Taking 0.3g of sodium chloride and 0.15g of potassium chloride, adding 10mL of water for injection, and stirring to dissolve to obtain a sodium chloride-potassium chloride solution for later use.
And (3) stirring and uniformly mixing the sodium chloride-potassium chloride solution and the edetate disodium solution to obtain a first solution for later use.
10mL of water for injection is taken, 0.2g of disodium hydrogen phosphate and 2g of boric acid are added, and stirred and dissolved to obtain a disodium hydrogen phosphate-boric acid solution.
Mixing the disodium hydrogen phosphate-boric acid solution with the first solution, adding 3g of diquafosol sodium (calculated by the diquafosol sodium), uniformly stirring, adding 2mL of sodium hydroxide with the concentration of 0.1mol/L to adjust the pH value to 7.99, and adding water for injection to 100mL to obtain the diquafosol sodium eye drops, wherein the final pH value is 7.96, and the osmotic pressure molar concentration ratio is 1.0.
Example 2
And adding 0.01g of edetate disodium into 70mL of injection water at the temperature of 30-35 ℃, and stirring to obtain an edetate disodium solution.
And adding 10mL of injection water into 0.4g of sodium chloride and 0.17g of potassium chloride, and stirring to dissolve to obtain a sodium chloride-potassium chloride solution for later use.
And (3) stirring and uniformly mixing the sodium chloride-potassium chloride solution and the edetate disodium solution to obtain a first solution for later use.
10mL of water for injection is taken, 0.3g of disodium hydrogen phosphate and 3g of boric acid are added, and stirred and dissolved to obtain a disodium hydrogen phosphate-boric acid solution.
And mixing the disodium hydrogen phosphate-boric acid solution with the first solution, adding 3g of diquafosol sodium (calculated by the diquafosol sodium), uniformly stirring, adding 2.5mL of 0.1mol/L sodium hydroxide aqueous solution to adjust the pH value to 7.98, and adding injection water to 100mL to obtain the diquafosol sodium eye drops, wherein the final pH value is 7.96 and the osmotic pressure molar concentration ratio is 1.0.
Example 3
And adding 0.015g of edetate disodium into 70mL of injection water at the temperature of 30-35 ℃, and stirring to obtain an edetate disodium solution.
Taking 0.5g of sodium chloride and 0.2g of potassium chloride, adding 10mL of water for injection, and stirring to dissolve to obtain a sodium chloride-potassium chloride solution for later use.
And (3) stirring and uniformly mixing the dissolved sodium chloride-potassium chloride solution and the edetate disodium solution to obtain a first solution for later use.
10mL of water for injection is taken, 0.4g of disodium hydrogen phosphate and 4g of boric acid are added, and stirred and dissolved to obtain a disodium hydrogen phosphate-boric acid solution.
And mixing the disodium hydrogen phosphate-boric acid solution with the first solution, adding 3g of diquafosol sodium (calculated by the diquafosol sodium), uniformly stirring, adding 3mL of a 0.1mol/L sodium hydroxide aqueous solution to adjust the pH value to 7.92, and adding water for injection to 100mL to obtain the diquafosol sodium eye drops, wherein the final pH value is 7.94, and the osmotic pressure molar concentration ratio is 1.0.
Comparative example 1
30g of diquafosol sodium, 5.0g of chitosan, 10.5g of boric acid and 2.88g of borax, and water is added to 100mL to obtain eye drops.
Comparative example 2
The differences from example 1 are: 0.005g of edetate disodium therein was replaced with 0.005g of boric acid.
Comparative example 3
The differences from example 1 are: 2g of boric acid therein was replaced with 2g of edetate disodium.
Comparative example 4
Eye drops available from Shentian pharmaceutical company under batch number MS 2570.
The eye drops obtained in examples 1 to 3 and comparative examples 1 to 4 were sealed in an eye drop bottle, and left to stand at 60 ℃ for 30 hours, and the change in pH of the obtained eye drops was observed, and the results are shown in Table 1.
The eye drops obtained in examples 1 to 3 and comparative examples 1 to 4 were sealed in an eye drop bottle at a strength of 1W/m2The eye drops were irradiated with the ultraviolet light of (1) under a daylight of 4500lx for 10 days, and the change in properties of the obtained eye drops was observed, with the results shown in Table 1.
TABLE 1 pH and shape changes of eye drops obtained in examples 1 to 3 and comparative examples 1 to 4
Experiment for inhibiting bacteria
The antibacterial activity of the eye drops obtained in examples 1 to 3 and comparative examples 1 to 4 was measured by an antibacterial efficacy test method of' Chinese pharmacopoeia 1121, 2020 edition, and the results are shown in Table 2.
TABLE 2 results of the bacteriostatic test on the eye drops obtained in examples 1 to 3 and comparative examples 1 to 4
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (5)
1. The diquafosol sodium eye drops are characterized by comprising the following components: diquafosol sodium, edetate disodium, disodium hydrogen phosphate, sodium chloride, potassium chloride, boric acid, a pH regulator and water;
the mass concentration of the sodium diquafosol is 3%;
the mass concentration of the edetate disodium is 0.005-0.015%;
the mass concentration of the disodium hydrogen phosphate is 0.2-0.4%;
the mass concentration of the sodium chloride is 0.3-0.5%;
the mass concentration of the potassium chloride is 0.15-0.2%;
the mass concentration of the boric acid is 2-4%;
the pH adjuster includes sodium hydroxide.
2. The diquafosol sodium eye drop solution as claimed in claim 1, wherein the pH value of the diquafosol sodium eye drop solution is 7.5-8.5.
3. The diquafosol sodium eye drop solution as claimed in claim 1, wherein the molar osmolality ratio of the diquafosol sodium eye drop solution is 1.0-1.1.
4. The diquafosol sodium eye drop of claim 1, wherein the water comprises water for injection.
5. The preparation method of diquafosol sodium eye drops as claimed in any one of claims 1 to 4, which is characterized by comprising the following steps:
dissolving edetate disodium in water to obtain edetate disodium solution;
dissolving sodium chloride and potassium chloride in water to obtain a sodium chloride-potassium chloride solution;
mixing the edetate disodium solution and a sodium chloride-potassium chloride solution to obtain a first solution;
dissolving disodium hydrogen phosphate and boric acid in water to obtain a disodium hydrogen phosphate-boric acid solution;
mixing the first solution, a disodium hydrogen phosphate-boric acid solution and sodium diquafosol to obtain a second solution;
and mixing the second solution and a pH regulating agent to obtain the diquafosol sodium eye drops.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210071074.9A CN114306228A (en) | 2022-01-21 | 2022-01-21 | Diquafosol sodium eye drops and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210071074.9A CN114306228A (en) | 2022-01-21 | 2022-01-21 | Diquafosol sodium eye drops and preparation method thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CN114306228A true CN114306228A (en) | 2022-04-12 |
Family
ID=81028855
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210071074.9A Pending CN114306228A (en) | 2022-01-21 | 2022-01-21 | Diquafosol sodium eye drops and preparation method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114306228A (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108853016A (en) * | 2018-09-26 | 2018-11-23 | 广州大光制药有限公司 | A kind of ophthalmic solution sodium eye drops and preparation method thereof |
CN112691080A (en) * | 2021-03-01 | 2021-04-23 | 南京恒道医药科技有限公司 | Diquafosol sodium composition, preparation and preparation method thereof |
-
2022
- 2022-01-21 CN CN202210071074.9A patent/CN114306228A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108853016A (en) * | 2018-09-26 | 2018-11-23 | 广州大光制药有限公司 | A kind of ophthalmic solution sodium eye drops and preparation method thereof |
CN112691080A (en) * | 2021-03-01 | 2021-04-23 | 南京恒道医药科技有限公司 | Diquafosol sodium composition, preparation and preparation method thereof |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP3256997B2 (en) | Stable aqueous formulation | |
US5403598A (en) | Physiological tear compositions and methods for their preparation | |
US5607698A (en) | Method of preserving ophthalmic solution and compositions therefor | |
JP3531945B2 (en) | Stable povidone-iodine ophthalmic solution | |
JP5620264B2 (en) | Phospholipid compositions for contact lens care and preserving pharmaceutical compositions | |
EP0824916B1 (en) | Pranoprofen eyedrops containing organic amine | |
NZ516969A (en) | Moxifloxacin formulation containing common salt | |
EP1324782B1 (en) | Stabilized ophthalmic hydrogen peroxide solutions | |
EP1905453B1 (en) | Preservative composition for ophthalmic use | |
EP0976407A1 (en) | Antiseptic composition | |
EP0354186B1 (en) | A method of preserving ophthalmic solutions and compositions therefor | |
JP2018177820A (en) | Aqueous ophthalmic composition | |
JP2916340B2 (en) | Aqueous pharmaceutical composition of sodium cromoglycate | |
CN114306228A (en) | Diquafosol sodium eye drops and preparation method thereof | |
JP4801300B2 (en) | Liquid composition for external use | |
JP5246182B2 (en) | Eye drops, preservatives and preservatives | |
KR20230145458A (en) | Aqueous pharmaceutical composition containing ursodeoxycholic acid or its salt | |
US10792271B2 (en) | Topical formulations of chloroprocaine and methods of using same | |
JP4524538B2 (en) | Ophthalmic composition | |
WO2019107569A1 (en) | Ophthalmic product | |
EP2419081B1 (en) | Aqueous ophthalmic compositions containing anionic therapeutic agents | |
US20100323978A1 (en) | Non-aqueous oil delivery system for ophthalmic drugs | |
EP2800573B1 (en) | Ophthalmic composition | |
USRE38628E1 (en) | Pharmaceutical compositions | |
GB2262448A (en) | Aqueous formulations of sodium cromoglycate |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |