CN114848587A - Nasal administration preparation containing agomelatine - Google Patents

Nasal administration preparation containing agomelatine Download PDF

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Publication number
CN114848587A
CN114848587A CN202210639712.2A CN202210639712A CN114848587A CN 114848587 A CN114848587 A CN 114848587A CN 202210639712 A CN202210639712 A CN 202210639712A CN 114848587 A CN114848587 A CN 114848587A
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agomelatine
parts
nasal administration
water
administration preparation
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罗熙
周群
曹娟
刘科
周叶文
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Hunan Huize Bio Pharmaceutical Co ltd
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Hunan Huize Bio Pharmaceutical Co ltd
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Abstract

The invention discloses a nasal administration preparation containing agomelatine, which comprises agomelatine, water, an absorption enhancer and a diluent; the diluent is selected from one or more of the following components: solvent, suspending agent, pH regulator, osmotic pressure regulator and vitamins. The nasal administration preparation provided by the invention has no irritation, is good in absorption, can avoid first-pass effect, and can improve brain concentration.

Description

Nasal administration preparation containing agomelatine
Technical Field
The invention relates to the technical field of agomelatine pharmaceutical compositions, and in particular relates to an agomelatine-containing nasal administration preparation.
Background
Agomelatine is a melatonin receptor agonist (MT) 1 And MT 2 Receptor) and 5-HT 2C Receptor antagonists have utility in the treatment of stress, sleep disorders, anxiety, seasonal depression, insomnia and fatigue due to jet lag, schizophrenia, panic attacks, melancholia, appetite regulation, insomnia and the like. Varying from 0.1mg to 1g over 24 hours depending on the age and weight of the patient, the route of administration or the indication to be treated.
Animal research results show that agomelatine can correct the circadian rhythm of the circadian rhythm disorder animal model and rebuild the rhythm. At present, agomelatine has only one dosage form of tablets, has a brand name of dimension new, and has a recommended dose of 25mg, which is taken before sleep 1 time per day. If symptoms do not improve after 2 weeks of treatment, the dose can be increased to 50mg 1 time per day.
Although the agomelatine tablets are quickly and well absorbed (more than or equal to 80%) after being orally taken, the agomelatine tablets belong to BCS II medicines, the water solubility is low, the absorption and curative effects of different regional groups are different, the serious first-pass effect exists, and the absolute bioavailability is extremely low (the oral therapeutic dose is less than 5%). The systemic exposure of agomelatine increases proportionally with increasing dose, within the therapeutic dose range. At high doses, the first-pass effect is saturated. Agomelatine has high hepatotoxicity, and liver function examination and reexamination are required to be performed regularly in the taking process.
The nasal cavity is used for administration, the nasal cavity is used for absorption through the nasal mucosa to play a local or systemic treatment role, the nasal mucosa has large surface area, loose and hydrophilic structure, contains a large amount of capillaries, and has quick drug absorption and quick response; convenient use and good patient compliance. In addition, part of the medicine can directly enter cerebrospinal fluid after being administrated, and has brain targeting effect. The nasal administration can reduce the generation of dysgeusia, avoid the first pass effect and greatly increase the bioavailability of the medicament. Meanwhile, nasal administration can also be directly connected into the brain along the olfactory nerve and trigeminal nerve pathways.
CN102579415A discloses a pharmaceutical composition containing agomelatine for oral mucosa or sublingual administration, which is prepared into a spray for oral or nasal mucosa administration, and is prepared into a film for oral mucosa or sublingual administration, but the stimulation feeling is strong.
The maximum amount of inactive ingredients of approved drugs published by the FDA for a single dose of ethanol in a spray was 198.8mg/mL, about 20% (https:// www.accessdata.fda.gov/scripts/cder/iig/index.cfm). In the prior art CN114028335A, a stable agomelatine nasal spray is disclosed, which is prepared by adding agomelatine, polyethylene glycol-6 methyl ether, metal ions and osmotic pressure regulator into ethanol-purified water solution, stirring and dissolving to obtain liquid medicine; wherein the ethanol content exceeds 60%, and the irritation is great. In addition, the content of ethanol in CN114028335A exceeds 60% when the conventional 75% ethanol is used as a disinfectant, and further proves that the provided formula has high irritation and is insufficient in the practical application process.
In view of the above, the present invention provides a nasal administration preparation containing agomelatine to reduce irritation of nasal administration.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a nasal administration preparation containing agomelatine, the nasal administration preparation has no irritation and good absorption, the nasal administration preparation avoids first-pass effect, and meanwhile, nasal-cerebral direct passage exists in the nose, so that the brain concentration can be further improved.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
according to an embodiment of the present invention, there is provided an agomelatine-containing nasal administration preparation, comprising agomelatine, water, an absorption enhancer and a diluent.
Furthermore, the nasal administration preparation containing agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 5-99 parts of water, 0-0.5 part of an absorption enhancer and 20-99 parts of a diluent.
Further, the agomelatine-containing nasal administration preparation has the ethanol content of less than 20%.
Further, the absorption enhancer is selected from dodecyl-beta-D-maltoside, dodecyl maltoside or octyl glucoside.
Further, the diluent is selected from one or more of the following components: solvent, suspending agent, pH regulator, osmotic pressure regulator and vitamins.
Further, the diluent is selected from one or more of the following components: 20-99 parts of solvent, 0-0.5 part of suspending agent, 0-0.5 part of pH regulator, 0-0.5 part of osmotic pressure regulator or 0-15 parts of vitamin.
Further, the suspending agent is one or more of sodium carboxymethylcellulose, tween 80, hydroxyethyl methylcellulose, carboxymethyl starch sodium, hydroxypropyl methylcellulose, and sodium carboxymethylcellulose-microcrystalline cellulose.
Further, the pH regulator is one or more of citric acid, hydrochloric acid, phosphoric acid, sodium hydroxide, potassium hydroxide, boric acid, borate, sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate.
Further, the osmotic pressure regulator is selected from one or more of sodium chloride, glycerol and potassium chloride.
Further, the vitamin is selected from one or more of vitamin E, vitamin B, vitamin C, vitamin K, vitamin A and vitamin D.
Further, the solvent is selected from one or more of polyethylene glycol (such as PEG400 and PEG600), propylene glycol, ethanol, methanol, acetonitrile and benzyl alcohol.
Furthermore, the agomelatine nasal administration preparation is prepared from 0.5-5.5 parts of agomelatine by weight; 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part, 1 part, 1.1 part, 1.2 parts, 1.3 parts, 1.4 parts, 1.5 parts, 1.6 parts, 1.7 parts, 1.8 parts, 2.0 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts or 5.5 parts of agomelatine.
Furthermore, the agomelatine nasal administration preparation comprises 0-0.35 part of absorption enhancer in parts by weight. Further, the absorption accelerator is 0, 0.02 part, 0.05 part, 0.08 part, 0.1 part, 0.15 part, 0.2 part, 0.23 part, 0.24 part, 0.25 part, 0.26 part, 0.27 part, 0.29 part, 0.30 part, 0.33 part or 0.35 part.
Furthermore, the agomelatine nasal administration preparation comprises, by weight, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 20 parts, 25 parts, 30 parts, 35 parts, 40 parts, 50 parts, 51 parts, 52 parts, 53 parts, 54 parts, 55 parts, 58 parts, 60 parts, 65 parts, 70 parts, 75 parts, 78 parts, 79 parts, 80 parts, 85 parts, 90 parts, 95 parts, 97 parts, 98 parts and 99 parts of water.
Furthermore, the agomelatine nasal administration preparation comprises 20 parts, 25 parts, 30 parts, 35 parts, 40 parts, 50 parts, 51 parts, 52 parts, 53 parts, 54 parts, 55 parts, 58 parts, 60 parts, 65 parts, 70 parts, 75 parts, 78 parts, 79 parts, 80 parts, 85 parts, 90 parts, 95 parts, 97 parts, 98 parts and 99 parts of solvent according to parts by weight. Further, the solvent is 20-55 parts.
Furthermore, the agomelatine nasal administration preparation comprises 0 part, 0.1 part, 0.2 part, 0.3 part, 0.4 part and 0.5 part of suspending agent in parts by weight.
Furthermore, the agomelatine nasal administration preparation comprises 0, 0.1 part, 0.2 part, 0.3 part, 0.4 part and 0.5 part of pH regulator according to parts by weight.
Furthermore, the agomelatine nasal administration preparation comprises, by weight, 0 part of osmotic pressure regulator, 0.01 part, 0.02 part, 0.05 part, 0.08 part, 0.1 part, 0.2 part, 0.3 part, 0.4 part and 0.5 part.
Furthermore, the agomelatine nasal administration preparation comprises, by weight, 0 part, 0.02 part, 0.05 part, 0.08 part, 0.1 part, 0.15 part, 0.2 part, 0.23 part, 0.24 part, 0.25 part, 0.26 part, 0.27 part, 0.29 part, 0.30 part, 0.33 part, 0.35 part, 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part, 1 part, 1.5 part, 2 parts, 2.5 parts, 3 parts, 4.5 parts, 5 parts, 5.5 parts, 6 parts, 6.5 parts, 7 parts, 7.5 parts, 8 parts, 8.5 parts, 9 parts, 9.5 parts, 10 parts, 10.5 parts, 11 parts, 11.5 parts, 12.5 parts, 13 parts, 13.5 parts, 14.5 parts and 15 parts of vitamins.
Further, the agomelatine nasal administration preparation comprises agomelatine, ethanol, PEG400, glycerol and water.
Further, the nasal administration preparation containing the agomelatine comprises agomelatine, ethanol, water and dodecyl-beta-D-maltose.
Further, the nasal administration preparation containing the agomelatine comprises agomelatine, ethanol, water, vitamins and dodecyl-beta-D-maltose.
Further, the nasal administration preparation containing agomelatine comprises agomelatine, Tween 80 and water.
Further, the nasal administration preparation containing agomelatine comprises agomelatine, Tween 80, water, dodecyl-beta-D-maltoside and ethanol.
Further, the agomelatine nasal administration preparation comprises agomelatine, ethanol, PEG400, propylene glycol, dodecyl-beta-D-maltoside and water.
Further, the agomelatine nasal administration preparation comprises agomelatine, ethanol, PEG400 and water.
Further, the agomelatine nasal administration preparation comprises agomelatine, PEG400 and water.
Furthermore, the agomelatine nasal administration preparation comprises, by weight, 0.5-10 parts of agomelatine, 0.01-0.5 part of glycerol, 10-25 parts of PEG40010, 30-80 parts of water and 1-20 parts of ethanol.
Furthermore, the nasal administration preparation containing agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 0.01-15 parts of ethanol, 50-97 parts of water and 0.01-0.5 part of dodecyl-B-D-maltoside.
Furthermore, the nasal administration preparation containing agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 0.01-15 parts of ethanol, 50-97 parts of water, 0.01-0.5 part of dodecyl-beta-D-maltoside and 0-15 parts of vitamins.
Furthermore, the nasal administration preparation containing agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 800.01-0.5 parts of tween and 20-90 parts of water.
Furthermore, the nasal administration preparation containing agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 800.01-0.5 parts of tween, 20-80 parts of water, 0.01-0.5 parts of dodecyl-beta-D-maltoside and 0-20 parts of ethanol.
Furthermore, the nasal administration preparation containing agomelatine comprises, by weight, 0.5-5 parts of agomelatine, 0-20 parts of ethanol, 0.5-0.5 part of PEG 4000.01, 0.01-10.5 parts of propylene glycol and 20-50 parts of water.
Furthermore, the nasal administration preparation containing agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 0-20 parts of ethanol, 78-15 parts of PEG 4000.01 and 50-97 parts of water.
Furthermore, the nasal administration preparation containing agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 4000.01-15 parts of PEG and 50-97 parts of water.
Further, the agomelatine is 0.5 part, 0.6 part, 0.7 part, 0.8 part, 0.9 part, 1 part, 1.1 part, 1.2 part, 1.25 part, 1.3 part, 1.35 part, 1.4 part, 1.45 part, 1.5 part, 1.6 part, 1.7 part, 2 part, 2.1 part, 2.2 part, 2.5 part, 3 part, 3.5 part, 4 part, 4.5 part, 5 part, 5.1 part, 5.2 part, 5.3 part, 5.4 part or 5.5 part.
Further, the content of the dodecyl-beta-D-maltoside is 0.02-0.5 part. Further, the dodecyl- β -D-maltoside is 0.02 parts, 0.05 parts, 0.10 parts, 0.15 parts, 0.20 parts, 0.24 parts, 0.25 parts, 0.26 parts, 0.27 parts, 0.29 parts, 0.30 parts, 0.33 parts, 0.35 parts, 0.4 parts, or 0.5 parts.
Further, the nasal administration preparation also comprises one or two of antioxidant and preservative. The antioxidant or the preservative accounts for 0.005-0.1 part of the total mass of the nasal administration preparation. Preferably, the antioxidant is selected from one or two of tert-butyl p-hydroxyanisole, butylated hydroxytoluene, vitamin C and vitamin E.
Furthermore, the nasal administration preparation is a spray, a nasal drop and a gel.
Furthermore, the specification of the nasal administration preparation is 0.5-5 mg/100 muL, and preferably 1mg/100 muL.
Compared with the prior art, the invention has the following beneficial technical effects:
the nasal administration preparation containing agomelatine prepared by the invention has low irritation and no toxicity, avoids first-pass effect and gastrointestinal degradation, improves bioavailability and reduces hepatotoxicity; one part is directly absorbed into blood through nasal mucosa and not absorbed into blood through hepatic portal vein, so that the concentration of liver tissue is reduced, and liver injury is reduced; the nose-brain has a direct and swift pathway, and can be directly accessed to the brain through olfactory nerves and trigeminal nerves.
Detailed Description
The technical solution of the present invention is illustrated below, and the claimed scope of the present invention includes, but is not limited to, the following examples.
Example 1
And sequentially adding 300mg of ethanol and 700mg of water into 10mg of agomelatine, and uniformly mixing.
Example 2
And sequentially adding 200mg of ethanol and 800mg of water into 10mg of agomelatine, and uniformly mixing.
Example 3
And sequentially adding 300mg of Tween 80 and 700mg of water into 10mg of agomelatine, and uniformly mixing to obtain the agomelatine.
Example 4
And sequentially adding 200mg of Tween 80 and 800mg of water into 10mg of agomelatine, and uniformly mixing to obtain the agomelatine.
Example 5
And sequentially adding 300mg of PEG400 and 700mg of water into 10mg of agomelatine, and uniformly mixing to obtain the agomelatine.
Example 6
Adding 200mg of ethanol, 200mg of PEG400 and 50mg of propylene glycol into 10mg of agomelatine in sequence, mixing uniformly, and adding 550mg of water to obtain the agomelatine.
Example 7
Adding 200mg of ethanol, 200mg of PEG400, 20mg of glycerol and 3.5mg of dodecyl-beta-D-maltoside into 10mg of agomelatine in sequence, mixing uniformly, and adding 580mg of water to obtain the agomelatine.
Example 8
Adding 200mg of ethanol, 10.5mg of vitamin B and 140mg of PEG400 into 10mg of agomelatine in sequence, adding 600mg of water, and uniformly mixing to obtain the agomelatine.
Example 9
And sequentially adding 180mg of ethanol, 180mg of PEG400 and 640mg of water into 10mg of agomelatine, and uniformly mixing to obtain the agomelatine.
Example 10
And sequentially adding 150mg of ethanol and 150mg of PEG400 into 10mg of agomelatine, uniformly mixing, and adding 700mg of water to obtain the agomelatine.
Example 11
Adding 85mg of ethanol, 750mg of water and 2.5mg of dodecyl-beta-D-maltoside into 10mg of agomelatine in sequence, and uniformly mixing to obtain the agomelatine.
Example 12
Adding 10.5mg of vitamin B, 950mg of water and 1.5mg of dodecyl-beta-D-maltoside into 10mg of agomelatine in sequence, and adding a proper amount of absolute ethyl alcohol until the total volume is 1mL to obtain the agomelatine.
Example 13
And sequentially adding 10.5mg of Tween 80, 500mg of water and 2.5mg of dodecyl-beta-D-maltoside into 10mg of agomelatine, and uniformly mixing to obtain the agomelatine.
Example 14
Adding 5mg of PEG400, 500mg of ethanol, 300mg of propylene glycol and 2.5mg of dodecyl-beta-D-maltoside into 10mg of agomelatine in sequence, and adding a proper amount of water until the total volume is 1mL to obtain the agomelatine.
Example 15
Adding 150mg of PEG400, 50mg of ethanol and 10mg of propylene glycol into 10mg of agomelatine in sequence, and adding a proper amount of water until the total volume is 1mL to obtain the agomelatine.
Example 16
Adding 10mg of PEG400, 50mg of ethanol and 20mg of glycerol into 10mg of agomelatine in sequence, and adding 580mg of water to obtain the agomelatine.
Example 17 irritation examination
The prepared sample is placed in a nasal cavity spraying device, the device is inserted into the nostril, and a valve is pressed to carry out irritation investigation. And scoring according to 0-5 points. 0: no irritation, 1: less irritating, 5: the irritation is great.
The results are shown in table 1:
TABLE 1 irritation test
Examples Scoring Examples Scoring
1 4 2 3
3 0 6 4
7 1 8 1
11 0 12 0
13 0 14 5
15 1 16 1
Through experiments of different formulas and component ratios, the irritability of the formula with larger irritability is mainly derived from ethanol. Irritation investigation shows that irritation reduction of the nasal administration preparation is achieved by reducing the proportion of ethanol and adding dodecyl-beta-D-maltoside or vitamins as a blend for alleviating or avoiding irritation of mucous membranes.
The combined formula of the invention has good spraying effect, meets the solubility, has few irritations and meets the requirements.
Example 18 PK study:
1. principle of design
The control test design between groups is adopted. The experiment adopts male and female half SD rats, and the rats are divided into groups. The body weight is between 250 and 300 g. Fasted overnight before the experiment and water was freely available.
2. Rat PK experiment
2.1 administration of drugs
Fasting was overnight before dosing and 4 hours after dosing, and water was available ad libitum.
Rats are randomly grouped, and the specific administration mode is as follows:
blank matrix group, oral drinking water;
in the control group, agomelatine tablet suspension is orally administered by intragastric gavage;
experimental group, nasal cavity is dripped with the nasal cavity administration preparation prepared in the embodiment of the application;
the administration was carried out at an equivalent dose of 2.5mg agomelatine/kg rat.
Consider the suspension of agomelatine tablets in gavage in rats (reference formulation R) or PK of a formulation for nasal administration (test formulation) prepared in the examples of the present application, instilled into the nasal cavity under fasting conditions.
2.2PK experiment (female and male halves)
About 0.5mL of jugular vein or orbital blood is collected 0h before administration and 0.083h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h and 12h after administration. The collected blood sample is anticoagulated by EDTA-K2 anticoagulant, and is centrifuged for 10min at 3500rpm at 2-8 ℃ within 1h after collection, and after plasma is separated, the blood sample is stored in a refrigerator at-80 ℃ for detection.
The results are shown in Table 2:
Tmax Cmax AUClast F
control group 0.25 22.02 26.01 -
Example 12 0.083 256.14 322.75 12.41
As can be seen from table 2, the bioavailability of agomelatine in the nasal administration preparation prepared by the invention is improved by 10-16 times, the individual difference is effectively reduced, the side effect is reduced, the drug effect equivalent to that of agomelatine tablets can be achieved under the condition of reducing the dose, and the liver toxicity can be further reduced.
Experiments show that the nasal administration preparation prepared by the invention has obviously improved distribution amount in the brain of a target organ for treatment, and reduced distribution amount in the liver of a toxic organ, thereby effectively avoiding first pass effect, improving treatment effect and reducing hepatotoxicity.

Claims (9)

1. A nasal administration preparation containing agomelatine is characterized by comprising agomelatine, water, an absorption enhancer and a diluent.
2. The formulation for nasal administration of agomelatine according to claim 1, wherein the diluent is selected from one or more of the following components: solvent, suspending agent, pH regulator, osmotic pressure regulator and vitamins.
3. The nasal administration preparation containing agomelatine according to claim 1, wherein the nasal administration preparation containing agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 5-99 parts of water, 0-0.5 part of an absorption enhancer and 20-99 parts of a diluent; the diluent is selected from one or more of the following components: 20-99 parts of solvent, 0-0.5 part of suspending agent, 0-0.5 part of pH regulator, 0-0.5 part of osmotic pressure regulator or 0-15 parts of vitamin.
4. The formulation for nasal administration of agomelatine according to claim 1, wherein said absorption enhancer is selected from dodecyl- β -D-maltoside, dodecyl maltoside or octyl glucoside;
the suspending agent is one or more of sodium carboxymethylcellulose, tween 80, hydroxyethyl methylcellulose, carboxymethyl starch sodium, hydroxypropyl methylcellulose, sodium carboxymethylcellulose-microcrystalline cellulose;
the pH regulator is one or more of citric acid, hydrochloric acid, phosphoric acid, sodium hydroxide, potassium hydroxide, boric acid, borate, sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate;
the osmotic pressure regulator is selected from one or more of sodium chloride, glycerol and potassium chloride;
the vitamins are selected from one or more of vitamin E, vitamin B, vitamin C, vitamin K, vitamin A and vitamin D;
the solvent is selected from one or more of polyethylene glycol, propylene glycol, ethanol, methanol, acetonitrile and benzyl alcohol.
5. The nasal formulation of agomelatine containing according to claim 4, wherein said nasal formulation of agomelatine comprises agomelatine, ethanol, PEG400, glycerol and water;
or, the nasal administration preparation containing agomelatine comprises agomelatine, ethanol, water and dodecyl-beta-D-maltose;
or, the nasal administration preparation containing agomelatine comprises agomelatine, ethanol, water, vitamins and dodecyl-beta-D-maltose;
or, the nasal administration preparation containing agomelatine comprises agomelatine, tween 80 and water;
or, the nasal administration preparation containing agomelatine comprises agomelatine, Tween 80, water, dodecyl-beta-D-maltoside and ethanol;
or the agomelatine nasal administration preparation comprises agomelatine, ethanol, PEG400, propylene glycol, dodecyl-beta-D-maltoside and water;
or, the agomelatine nasal administration preparation comprises agomelatine, ethanol, PEG400 and water;
or the agomelatine nasal administration preparation comprises agomelatine, PEG400 and water.
6. The nasal administration preparation containing agomelatine according to claim 5, wherein the nasal administration preparation contains 0.5-10 parts by weight of agomelatine, 0.01-0.5 part by weight of glycerol, 10-25 parts by weight of PEG40010, 30-80 parts by weight of water and 1-20 parts by weight of ethanol;
or the nasal administration preparation containing the agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 0.01-15 parts of ethanol, 50-97 parts of water and 0.01-0.5 part of dodecyl-beta-D-maltoside;
or the nasal administration preparation containing agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 0.01-15 parts of ethanol, 50-97 parts of water, 0.01-0.5 part of dodecyl-beta-D-maltoside and 0-15 parts of vitamins;
or the nasal administration preparation containing the agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 800.01-0.5 parts of tween and 20-90 parts of water;
or the nasal administration preparation containing agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 800.01-0.5 parts of tween, 20-80 parts of water, 0.01-0.5 parts of dodecyl-beta-D-maltoside and 0-20 parts of ethanol;
or the nasal administration preparation containing agomelatine comprises, by weight, 0.5-5 parts of agomelatine, 0-20 parts of ethanol, 0.5-0.5 part of PEG 4000.01, 0.01-10.5 parts of propylene glycol and 20-50 parts of water;
or the nasal administration preparation containing the agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 0-20 parts of ethanol, 4000.01-15 parts of PEG and 50-97 parts of water;
or the nasal administration preparation containing the agomelatine comprises, by weight, 0.5-10 parts of agomelatine, 4000.01-15 parts of PEG and 50-97 parts of water.
7. The nasal formulation of claim 6, wherein the formulation further comprises one or both of an antioxidant and a preservative.
8. A formulation for nasal administration containing agomelatine according to claim 1, characterised in that it is a spray, nasal drops or gel.
9. The nasal delivery preparation containing agomelatine according to claim 1, wherein the specification of the nasal delivery preparation is 0.5-5 mg/100 μ L.
CN202210639712.2A 2022-06-08 2022-06-08 Nasal administration preparation containing agomelatine Pending CN114848587A (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102579415A (en) * 2011-01-14 2012-07-18 成都康弘药业集团股份有限公司 Agomelatine-containing medicinal composition for oral mucosa or sublingual administration
CN114028335A (en) * 2021-12-24 2022-02-11 山东京卫制药有限公司 Agomelatine solution nasal spray and application thereof
CN114366714A (en) * 2021-04-29 2022-04-19 山东京卫制药有限公司 Agomelatine suspension nasal spray and application thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102579415A (en) * 2011-01-14 2012-07-18 成都康弘药业集团股份有限公司 Agomelatine-containing medicinal composition for oral mucosa or sublingual administration
CN114366714A (en) * 2021-04-29 2022-04-19 山东京卫制药有限公司 Agomelatine suspension nasal spray and application thereof
CN114028335A (en) * 2021-12-24 2022-02-11 山东京卫制药有限公司 Agomelatine solution nasal spray and application thereof

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AHMED M FATOUH等: "Intranasal agomelatine solid lipid nanoparticles to enhance brain delivery:formulation, optimization and in vivo pharmacokinetics", 《DRUG DESIGN, DEVELOPMENT AND THERAPY》 *
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