CN-122005453-A - Orostatin and budesonide composition nasal spray and preparation method thereof

Abstract

The invention discloses an olopatadine and budesonide composition nasal spray and a preparation method thereof, and relates to the technical field of pharmaceutical preparations, wherein the oral spray comprises 0.03-0.3% (w/v) budesonide, 0.05-5% (w/v) olopatadine, 0.05-4% (w/v) suspending agent, 0.001-0.05% (w/v) metal ion chelating agent, 0.05-10% (w/v) osmotic pressure regulator, 0.01-1% (w/v) absorption promoting osmotic agent, 0.008-0.128% (w/v) surfactant, and 0.002-0.2% (w/v) bacteriostatic agent. The olopatadine and budesonide composition nasal spray not only improves the treatment effect of rhinitis, but also has very high temperature during storage, and the fluidity and atomization performance of liquid medicine are also very good.

Inventors

• LIU PENG
• ZHANG QIAN
• HE GANGMIN
• LI HONGYANG

Assignees

• 江苏德迈药业有限公司

Dates

Publication Date

20260512

Application Date

20260320

Claims (10)

1. 1. The nasal spray of the olopatadine and budesonide composition is characterized by comprising 0.03% (w/v) -0.3% (w/v) budesonide, 0.05% (w/v) -5% (w/v) olopatadine, 0.05% (w/v) -4% (w/v) suspending agent, 0.001% (w/v) -0.05% (w/v) metal ion chelating agent, 0.05% (w/v) -10% (w/v) osmotic pressure regulator, 0.01% (w/v) -1% (w/v) absorption promoting osmotic agent, 0.008% (w/v) -0.128% (w/v) surfactant, 0.002% (w/v) -0.2% (w/v) bacteriostatic agent and water as solvent.
2. 2. A nasal spray of an olopatadine and budesonide composition according to claim 1, wherein the suspending agent comprises any one or more of pectin, microcrystalline cellulose sodium carboxymethyl cellulose, hypromellose, povidone.
3. 3. A nasal spray of an olopatadine and budesonide composition according to claim 1, wherein the metal ion chelating agent comprises an ethylenediamine tetraacetic acid based compound.
4. 4. A nasal spray of an olopatadine and budesonide composition according to claim 1, wherein the osmotic pressure regulator comprises any one or more of mannitol, glucose, glycerol, sodium chloride.
5. 5. A nasal spray of an olopatadine and budesonide composition according to claim 1, wherein the absorption enhancing osmotic agent comprises any one or more combinations of dodecyl β -D-maltoside, tetradecyl maltoside, dodecyl phosphorylcholine.
6. 6. The nasal spray of an olopatadine and budesonide composition according to claim 1, wherein a pH regulator is further added for regulating the pH of the spray composition to 4.0-7.0.
7. 7. The nasal spray of olopatadine and budesonide composition according to claim 6, wherein the pH adjuster comprises any one or more of citric acid, sodium citrate, acetic acid, sodium acetate, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium hydroxide, hydrochloric acid, and sulfuric acid.
8. 8. A method for preparing a nasal spray of an olopatadine and budesonide composition, which is characterized by comprising the following steps: Preparing a suspending agent, namely adding purified water into a liquid preparation tank, slowly adding the suspending agent under stirring and/or high shearing state, continuously stirring and dispersing for 1-6 hours at the temperature of 80-100 ℃ after uniform dispersion, then cooling, and circularly shearing for 5-20 minutes; Preparing budesonide suspension, namely preparing a metal ion chelating agent and a surfactant into a solution, adding budesonide, stirring and wetting, and transferring to a liquid preparation tank for dispersion treatment; Preparing solution materials, namely adding purified water into a liquid preparation tank, adding pH buffer salt, a bacteriostatic agent, an osmotic pressure regulator and an absorption promoting osmotic agent, stirring and dissolving, continuously adding olopatadine, and stirring and dissolving to obtain liquid medicine; adding the liquid medicine and the budesonide suspension into a suspending agent, stirring uniformly, adjusting the pH to 4.0-7.0 by adopting a pH regulator, adding water to the full amount, and stirring uniformly to obtain the nasal spray.
9. 9. A process for the preparation of a nasal spray of an olopatadine and budesonide composition according to claim 8, wherein the suspending agent is formulated such that the temperature after agitation and dispersion is reduced to no more than 40 ℃.
10. 10. The method for preparing the nasal spray of the olopatadine and budesonide composition according to claim 8, wherein the dispersion treatment mode of the budesonide suspension preparation comprises ultrasonic dispersion or wetting dispersion of the budesonide under high-speed shearing conditions.

Description

Orostatin and budesonide composition nasal spray and preparation method thereof Technical Field The invention relates to the technical field of pharmaceutical preparations, in particular to an olopatadine and budesonide composition nasal spray and a preparation method thereof. Background Olopatadine is a second generation antihistamine drug, belonging to the selective histamine H 1 receptor antagonist ‌, and is mainly used for relieving symptoms of allergic diseases. Its core functions include relieving itching, red swelling, sneeze, watery nasal discharge, etc. caused by allergic rhinitis and urticaria, and anti-inflammatory effect. Olopatadine oral formulations (tablets, capsules, granules) and olopatadine eye drops have been marketed. The olopatadine oral preparation is mainly used for treating allergic rhinitis, urticaria, pruritic dermatosis (eczema, dermatitis, prurigo, skin pruritus, psoriasis vulgaris, exudative polymorphous erythema). Olopatadine eye drops are mainly used for treating signs and symptoms of allergic conjunctivitis. When olopatadine is used for treating rhinitis, for example, the olopatadine is orally administered, the dosage of the olopatadine is relatively large (5 mg/time), the occurrence rate of side effects is relatively high due to the systemic effect of the drug, such as sleepiness (dangerous mechanical operations affecting driving and the like), liver damage or other biochemical index changes, and myocardial infarction is reported. When it is applied as a nasal spray, it is effective locally, and its dosage is relatively low, so that side effects caused by systemic effects can be avoided. Budesonide is a glucocorticoid having a potent local anti-inflammatory effect. The glucocorticoid receptor affinity is about 15 times higher than that of prednisolone, has high-efficiency anti-inflammatory effect, and can inhibit the release of inflammatory mediators and inhibit cytokine-mediated immune response. Is mainly used for treating seasonal and perennial allergic rhinitis and perennial non-allergic rhinitis, preventing the regeneration of nasal polyp after nasal polyp excision and symptomatically treating nasal polyp. However, both olopatadine alone and budesonide alone have limited therapeutic efficacy in the treatment of rhinitis. Disclosure of Invention Based on the problem that the prior art has poor treatment effect when the olopatadine and the budesonide are directly used for treating rhinitis, the invention aims to provide the olopatadine and budesonide composition nasal spray and the preparation method thereof, which not only improve the treatment effect of rhinitis, but also ensure that the spray composition is stable during storage and has good liquid medicine fluidity and atomization performance. The invention is realized by the following technical scheme: In a first aspect, the application provides an olopatadine and budesonide composition nasal spray, which comprises 0.03% (w/v) -0.3% (w/v) budesonide, 0.05% (w/v) -5% (w/v) olopatadine, 0.05% (w/v) -4% (w/v) suspending agent, 0.001% (w/v) -0.05% (w/v) metal ion chelating agent, 0.05% (w/v) -10% (w/v) osmotic pressure regulator, 0.01% (w/v) -1% (w/v) absorption promoting osmotic agent, 0.008% (w/v) -0.128% (w/v) surfactant, 0.002% (w/v) -0.2% (w/v) bacteriostatic agent, and water as solvent. The olopatadine is used as a selective histamine H 1 receptor antagonist, can block anaphylactic reactions such as vasodilation, permeability increase and the like caused by histamine, can stabilize mast cell membranes, prevent degranulation and release inflammatory mediators such as histamine and the like, thereby relieving symptoms such as nasal itching, sneeze, watery nasal discharge and the like, and budesonide is a glucocorticoid with high-efficiency local anti-inflammatory effect, and can inhibit release of inflammatory mediators and cytokine-mediated immune response. The two can play a synergistic role in treating allergic rhinitis and enhance the curative effect of the medicine. The added suspending agent can increase the viscosity of the medicine and provide thixotropic property, thus prolonging the retention time of the medicine at the administration position and enhancing the curative effect of the medicine, the added metal ion chelating agent can inhibit the degradation of the medicine in an aqueous environment and ensure the physicochemical stability of the medicine preparation during storage, and the added absorption promoting penetrating agent can promote the absorption of the medicine and assist the suspending agent to lead the medicine to have the retention effect at the administration position, thus enhancing the curative effect. In a specific embodiment, the suspending agent comprises any one or more of pectin, microcrystalline cellulose sodium carboxymethyl cellulose, hypromellose, and povidone. In a specific embodiment, the metal ion chelating agent comprises ethylenediamine tetraacetic acid based compounds, incl