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`[19] The State Intellectual Property Office of the People’s Republic of China
`
`[51] Int. Cl7
`A61K 31/485
`A61K 9/12 A61P 39/02
`
`[12] Published Specification of Application for Patent for Invention
`
`[21] Application no.: 200410049659.2
`
`[43] Publication date: February 9, 2005
`
`[11] Publication No.: CN 1575795 A
`
`[74] Patent agency: CCPIT Patent and
`Trademark Law Office
`
`Patent agent: TANG Weijie
`
`[22] Date of filing: June 23, 2004
`[21] Application no.: 200410049659.2
`[30] Priority
`[32] June 25, 2003 [33] CN [31] 03147840.9
`[71] Applicant: Institute of Pharmacology and
`Toxicology, Academy of Military Medical Sciences
`P.L.A. China
`Address: No. 27, Taiping Road, Haidian
`District, Beijing, 100850.
`[72] Inventors: WANG Weixian, GAO Lijun, MEI
`Xingguo
`
`Claims: 1 pages
`
`Description: 2 pages
`
`[54] Title of invention
`Nasal Spray of Naloxone Hydrochloride
`[57] Abstract
`The present invention relates to a nasal spray of
`naloxone hydrochloride and a preparation method
`thereof. The preparation of the present invention can
`be used in single-dose and multi-dose forms. The
`spray of the present invention comprises naloxone
`hydrochloride, an osmotic pressure regulator, a
`preservative, a penetration enhancer and water.
`
`Published by Intellectual Property Publishing House
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`200410049659.2
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`Claims
`
`Page 1 of 1
`
`spray of naloxone hydrochloride, comprising naloxone
`1. A nasal
`hydrochloride, an osmotic pressure regulator, a penetration enhancer, a
`preservative and water.
`2. The nasal spray of claim 1, wherein the osmotic pressure regulator is
`selected from sodium chloride, potassium nitrate, boric acid, and glucose.
`3. The nasal spray of claim 1 or 2, wherein the preservative is selected
`from methyl, ethyl, propyl, or butyl para-hydroxybenzoate, sorbic acid, sodium
`sorbate, benzoic acid, sodium benzoate, benzyl alcohol, benzalkonium chloride,
`benzalkonium bromide, chlorobutanol, resorcinol and sodium ethylenediamine
`tetraacetate.
`4. The nasal spray of claims 1-3, wherein the penetration enhancer
`
`comprises(cid:3)(cid:3)(cid:6917) organic solvents such as alcohols, esters, dimethyl sulfoxide and
`
`homologues thereof; (cid:312)(cid:3)fatty acids, fatty alcohols and cholates; (cid:313)(cid:3)laurocapram
`(cid:68)(cid:81)(cid:71)(cid:3)homologues thereof; (cid:314) surfactants such as cationic, anionic, nonionic and
`lecithin surfactants; (cid:315) terpenes; and (cid:316) horny layer moisturizing and softening
`agents.
`5. The nasal spray of any of claims 1-4, wherein the preservative is ethyl
`para-hydroxybenzoate.
`6. The nasal spray of claim 5, wherein the osmotic pressure regulator is
`sodium chloride.
`7. The nasal spray of claim 6, wherein the penetration enhancer is
`propylene glycol.
`8. The nasal spray of claim 7, wherein the water is water for injection, or
`an alcohol which can be mixed with water such as propylene glycol, glycerol, and
`ethanol, and an ester.
`spray of any of claims 1-4, wherein the naloxone
`9. The nasal
`hydrochloride is administered in a single dose of 0.1-10 mg.
`10. The nasal spray of any of claims 1-4, wherein the spray has a particle
`size of 5-200 μm.
`11. The nasal spray of any of claims 1-4, wherein the spray is a spray in a
`single-dose or multi-dose form.
`12. The nasal spray of any of claims 1-4, wherein the nasal spray has a pH
`of 3.0-4.5.
`
`(cid:24)
`
`(cid:20)(cid:19)
`
`(cid:20)(cid:24)
`
`(cid:21)(cid:19)
`
`(cid:21)(cid:24)
`
`(cid:22)(cid:19)
`
`2
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`200410049659.2
`
`Description
`
`Page 1 of 2
`
`Nasal Spray of Naloxone Hydrochloride
`
`(cid:24)
`
`(cid:20)(cid:19)
`
`(cid:20)(cid:24)
`
`(cid:21)(cid:19)
`
`(cid:21)(cid:24)
`
`(cid:22)(cid:19)
`
`(cid:22)(cid:24)
`
`(cid:23)(cid:19)
`
`Technical Field
`The present invention relates to a nasal spray of naloxone hydrochloride and
`a preparation method thereof. The present
`invention further relates to a
`single-dose and multi-dose nasal spray of naloxone hydrochloride. The nasal
`spray of the present invention comprises naloxone hydrochloride, an osmotic
`pressure regulator, a preservative, a penetration enhancer and water.
`Background Art
`Naloxone hydrochloride is a morphine antagonist and can be used for first
`aid for morphine drug poisoning, rescue for acute alcoholism and the like. The
`drug is clinically used in the forms of injections and sublingual tablets; however,
`the injections are usually used in hospitals or clinics, and both the injections and
`sublingual tablets have problems of inconvenient use and poor compliance,
`thereby reducing the efficacy and influencing absorption and bioavailability.
`Summary of the Invention
`The object of the present invention is to overcome the shortcomings of the
`current preparations of naloxone hydrochloride injections and sublingual tablets,
`and to develop a novel single-dose and multi-dose nasal spray of naloxone
`hydrochloride which can be used by the patients themselves or used with the aid
`of others, with rapid absorption, high bioavailability, convenient use, and no need
`of special conditions.
`The inventors have found through intensive studies that a novel nasal spray
`administration dosage form is formed by mixing naloxone hydrochloride with an
`optional preservative, osmotic pressure regulator, penetration enhancer and
`water. The preparation has a single-dose and multi-dose nasal spray with rapid
`absorption, high bioavailability and low irritation. The preparation is suitable for
`scale production and storage.
`Accordingly, a first aspect of the invention relates to a naloxone-containing
`nasal
`spray preparation for nasal administration,
`comprising naloxone
`hydrochloride, an osmotic pressure regulator, a preservative, a penetration
`enhancer and water.
`the naloxone
`the invention relates to the use of
`Another aspect of
`hydrochloride-containing nasal spray for the relief or treatment in first aid for
`morphine drug poisoning, acute alcoholism and the like.
`According to the present invention, the preservative used in the nasal spray
`the present
`invention is selected from methyl, ethyl, propyl, or butyl
`of
`para-hydroxybenzoate, sorbic acid, benzoic acid, sodium benzoate, benzyl
`alcohol,
`benzalkonium chloride,
`benzalkonium bromide,
`chlorobutanol,
`resorcinol, sodium ethylenediamine tetraacetate and the like; and the osmotic
`pressure regulator is selected from sodium chloride, potassium nitrate, boric acid,
`
`and glucose. The penetration enhancer is selected from(cid:3)(cid:3)(cid:6917) organic solvents such
`
`as alcohols, esters, dimethyl sulfoxide and homologues thereof; (cid:312)(cid:3)fatty acids,
`fatty alcohols and cholates; (cid:313) laurocapram and homologues thereof; (cid:314)
`1
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`200410049659.2
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`Description
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`Page 2 of 2
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`surfactants such as cationic, anionic, nonionic and lecithin surfactants; (cid:315)
`terpenes; and (cid:316) horny layer moisturizing and softening agents.
`two
`The present
`invention further provides a preparation method of
`naloxone hydrochloride-containing nasal sprays, comprising: mixing naloxone
`hydrochloride, a preservative, an osmotic pressure regulator, a penetration
`enhancer with water for injection to dissolve them, adjusting the pH to 3.0-4.5,
`filtered, and then filling single-dose and multi-dose nasal spray devices with the
`solution separately.
`The present invention comprises naloxone hydrochloride with a content of
`0.1%-10.0% by weight, and an osmotic pressure regulator, a preservative and
`water with a content of 94.0%-99.9% by weight based on the weight of the spray
`liquid; and the spray has a particle size of 5 to 200 μm.
`The nasal spray of the present invention is used in a single-dose or multi-dose
`form, and the administration amount of the nasal spray is 20-200 μl each time.
`The following examples are provided to further illustrate the invention but
`are not meant to limit the invention in any way.
`Example 1 Preparation of a nasal spray of naloxone hydrochloride.
`0.03 g of ethyl para-hydroxybenzoate was weighed, and placed in a 100 ml
`volumetric flask, to which an appropriate amount of water for injection was
`added, followed by dissolving them by heating in a warm water bath, cooling to
`room temperature, then adding 1.0 g of naloxone hydrochloride dry product and
`0.9 g of sodium chloride, shaking to dissolve, adding water for injection close to
`the scale mark, shaking uniformly, adjusting to a pH value of 3.8 ± 0.8 with 0.1
`mol/L hydrochloric acid, adding water for injection to the scale mark, shaking
`uniformly, and filtering with 0.25 μm microporous filter membrane until the drug
`liquid is
`clear,
`thereby obtaining the nasal
`spray liquid of naloxone
`hydrochloride. Subsequently, single-dose and multi-dose nasal spray devices were
`filled with the nasal spray liquid separately and packaged for later use.
`Example 2 Preparation of a nasal spray of naloxone hydrochloride.
`0.03 g of ethyl para-hydroxybenzoate was weighed, and placed in a 100 ml
`volumetric flask, to which 20 g of propylene glycol was added and then an
`appropriate amount of water for injection was added, followed by dissolving them
`by heating in a warm water bath, cooling to room temperature, then adding 1.0 g
`of naloxone hydrochloride dry product and 0.9 g of sodium chloride, shaking to
`dissolve, adding water for injection close to the scale mark, shaking uniformly,
`adjusting to a pH value of 3.8 ± 0.8 with 0.1 mol/L hydrochloric acid, adding
`water for injection to the scale mark, shaking uniformly, and filtering with 0.25
`μm microporous filter membrane until the drug liquid is clear, thereby obtaining
`the nasal spray liquid of naloxone hydrochloride. Subsequently, single-dose and
`multi-dose nasal spray devices were filled with the nasal spray liquid separately
`and packaged for later use.
`
`(cid:24)
`
`(cid:20)(cid:19)
`
`(cid:20)(cid:24)
`
`(cid:21)(cid:19)
`
`(cid:21)(cid:24)
`
`(cid:22)(cid:19)
`
`(cid:22)(cid:24)
`
`(cid:23)(cid:19)
`
`2
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`(cid:11105)(cid:3)(cid:6299)(cid:6655)(cid:1944)(cid:14125)(cid:10683)(cid:3)(cid:6299)(cid:6655)(cid:2123)(cid:5418)
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`11/18/2018
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`CN1575795 Naloxone hydrochloride nasal spray
`
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`Machine translation
`  
`3. (CN1575795) Naloxone hydrochloride nasal spray
`
`National Biblio. Data
`
`Description
`
`Claims
`
`Documents
`
`PermaLink
`
`  
`
`
`
`Application Number: 200410049659.2 Application Date: 23.06.2004
`Publication Number: 1575795 Publication Date: 09.02.2005
`Publication Kind : A
`IPC:
`A61K 9/12
`
`A61K 31/485
`Toxic Pharmaceutics Inst., P.L.A. Academy of Military Medical Sciences
`中国人民解放军军事医学科学院毒物药物研究所
`Wang Weixiang
`王维贤
`Gao Lijun
`高立军
`Mei Xingguo
`梅兴国
`tang weijie
`中国国际贸易促进委员会专利商标事务所
`
`Applicants:
`
`Inventors:
`
`Agents:
`
`Priority Data:
`Title:
`
`Abstract:
`
`(EN) Naloxone hydrochloride nasal spray
`(ZH) 盐酸纳洛酮鼻腔喷雾剂
`(EN) The present invention is nasal cavity spray of Naloxine hydrochloride and its preparation process. The preparation of the present invention
`may be applied in single dosage form or multiple dosage form. The spray of the present invention includes Naloxine hydrochloride, osmotic
`pressure regulator, preservative, osmotic promoter and water.
`(ZH)
`
`本发明涉及盐酸纳洛酮的鼻腔喷雾剂及制备方法，本发明制剂可以单剂量及多剂量形式使用。本发明喷雾剂包括盐酸纳洛酮、渗透压调节剂、防腐
`剂、渗透促进剂及水。
`
`https://patentscope.wipo.int/search/en/detail.jsf?docId=CN82769597&tab=NATIONALBIBLIO&office=&prevFilter=&sortOption=Pub+Date+Desc&query… 1/1
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