US4464378A
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Method of administering narcotic antagonists and analgesics and novel dosage forms containing same
Assignee: KENTUCK LEXINGTON KY, University of, Trustees of
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Filing: 1981-04-28
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Granted: 1984-08-07
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Expires: 2001-04-28
Abstract
Abstract The invention provides a novel method of administering narcotic antagonists, narcotic analgesics and related compounds, and novel dosage forms containing those compounds which are adapted for nasal administration. The nasal dosage forms disclosed include solutions, suspensions, gels and ointments. Especially preferred compounds which can be advantageously administered in accordance with the invention include naloxone, naltrexone, nalbuphine, levorphanol, buprenorphine, butorphanol, DELTA 9-tetrahydrocannabinol (THC), cannabidiol (CBD) and levonantradol.
Inventors
- 👤 Anwar A. Hussain
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 07:11
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/335; A61K31/35; A61K31/395; A61K31/435; A61K31/47; A61K31/485; A61K9/00; A61K9/0012; A61K9/0043
Claims Analysis
Total Claims: 55
Claim 1
Independent Claim
101 words
A method for eliciting an analgesic or narcotic antagonist response in a warm-blooded animal, which comprises nasally administering to said animal: (a) to elicit an analgesic response, an analgesically effective amount of morphine, hydromorphone, metopon, oxymorphone, desomorphine, dihydromorphine, levorphanol, cyclazocine, phenazocine, levallorphan, 3-hydroxy-N-methylmorphinan, levophenacylmorphan, metazocine, norlevorphanol, phenomorphan, nalorphine, nalbuphine, buprenorphine, butorphanol or pentazocine, or a nontoxic pharmaceutically acceptable acid addition salt thereof; or (b) to elicit a narcotic antagonist response, a narcotic antagonist effective amount of naloxone, naltrexone, diprenorphine, nalmexone, cyprenorphine, levallorphan, alazocine, oxilorphan, cyclorphan, nalorphine, nalbuphine, buprenorphine, butorphanol, cyclazocine or pentazocine, or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 2
Independent Claim
101 words
A method for eliciting an analgesic or narcotic antagonist response in a warm-blooded animal, which comprises nasally administering to said animal: (a) to elicit an analgesic response, an analgesically effective amount of morphine, hydromorphone, metopon, oxymorphone, desomorphine, dihydromorphine, levorphanol, cyclazocine, phenazocine, levallorphan, 3-hydroxy-N-methylmorphinan, levophenacylmorphan, metazocine, norlevorphanol, phenomorphan, nalorphine, nalbuphine, buprenorphine, butorphanol or pentazocine, or a nontoxic pharmaceutically acceptable acid addition salt thereof; or (b) to elicit a narcotic antagonist response, a narcotic antagonist effective amount of naloxone, naltrexone, diprenorphine, nalmexone, cyprenorphine, levallorphan, alazocine, oxilorphan, cyclorphan, nalorphine, nalbuphine, buprenorphine, butorphanol, cyclazocine or pentazocine, or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 3
Dependent Claim
54 words
A method according to claim 1 for eliciting a narcotic antagonist response in a warm-blooded animal, which comprises nasally administering to said animal a narcotic antagonist effective amount of naxolone, naltrexone, diprenorphine, nalmexone, cyprenorphine, levallorphan, alazocine, oxilorphan, cyclorphan, nalorphine, nalbuphine, buprenorphine, butorphanol, cyclazocine or pentazocine, or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 4
Dependent Claim
29 words
The method according to claim 2 wherein the compound administered is naloxone, naltrexone, nalorphine, nalbuphine, buprenorphine, diprenorphine, nalmexone or cyprenorphine, or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 5
Dependent Claim
34 words
The method according to claim 2 wherein the compound administered is in the form of a long-chain carboxylic acid salt, the carboxylic acid portion of the salt containing from 10 to 20 carbon atoms.
Claim 6
Dependent Claim
19 words
The method according to claim 4 wherein the long chain carboxylic acid salt is a stearate, palmitate or myristate.
Claim 7
Dependent Claim
21 words
The method according to claim 3 wherein the compound administered is naloxone or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 8
Dependent Claim
21 words
The method according to claim 3 wherein the compound administered is naltrexone or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 9
Dependent Claim
21 words
The method according to claim 3 wherein the compound administered is nalorphine or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 10
Dependent Claim
21 words
The method according to claim 3 wherein the compound administered is nalbuphine or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 11
Dependent Claim
21 words
The method according to claim 3 wherein the compound administered is buprenorphine or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 12
Dependent Claim
44 words
A method according to claim 1 for eliciting an analgesic response in a warm-blooded animal which comprises nasally administering to said animal an analgesically effective amount of nalorphine, nalbuphine, buprenorphine, butorphanol, cyclazocine, levallorphan or pentazocine, or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 13
Dependent Claim
35 words
The method according to claim 11 wherein the compound administered is in the form of a long chain carboxylic acid salt, the carboxylic acid portion of the salt containing from 10 to 20 carbon atoms.
Claim 14
Dependent Claim
19 words
The method according to claim 12 wherein the long chain carboxylic acid salt is a stearate, palmitate or myristate.
Claim 15
Dependent Claim
21 words
The method according to claim 11 wherein the compound administered is buprenorphine or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 16
Dependent Claim
50 words
A method according to claim 1 for eliciting an analgesic response in a warm-blooded animal, which comprises nasally administering to said animal an analgesically effective amount of morphine, hydromorphone, metopon, oxymorphone, desomorphine, dihydromorphine, levorphanol, phenazocine, 3-hydroxy-N-methylmorphinan, levophenacylmorphan, metazocine, norlevorphanol or phenormorphan, or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 17
Dependent Claim
26 words
The method according to claim 15 wherein morphine is administered, in the form of the free base or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 18
Dependent Claim
38 words
The method according to claim 15 wherein hydromorphone, metopon, oxymorphone, desomorphine, dihydromorphine, levorphanol, phenazocine, 3-hydroxy-N-methylmorphinan, levophenacylmorphan, metazocine, norlevorphanol or phenomorphan is administered, in the form of the free base or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 19
Dependent Claim
24 words
The method according to claim 17 wherein the compound administered is hydromorphone, metopon or oxymorphone, or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 20
Dependent Claim
35 words
The method according to claim 15 wherein the compound administered is in the form of a long chain carboxylic acid salt, the carboxylic acid portion of the salt containing from 10 to 20 carbon atoms.
Claim 21
Dependent Claim
25 words
A method according to claim 2 wherein the compound administered is butorphanol, pentazocine, cyclazocine or oxilorphan, or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 22
Dependent Claim
21 words
The method according to claim 20 wherein the compound administered is butorphanol or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 23
Dependent Claim
24 words
A method according to claim 11 wherein the compound administered is butorphanol, cyclazocine or pentazocine, or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 24
Dependent Claim
21 words
The method according to claim 17 wherein the compound administered is levorphanol or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 25
Dependent Claim
33 words
The method according to claim 1 wherein the compound administered is morphine, oxymorphone, buprenorphine, naloxone, nalorphine, nalbuphine, naltrexone, hydromorphone, metopon, nalmexone, cyprenorphine or diprenorphine, or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 26
Dependent Claim
33 words
The method according to claim 24 wherein the compound is in the form of a long-chain carboxylic acid salt, the carboxylic acid portion of the salt containing from 10 to 20 carbon atoms.
Claim 27
Dependent Claim
18 words
The method according to claim 25 wherein the long-chain carboxylic acid salt is a stearate, palmitate or myristate.
Claim 28
Dependent Claim
27 words
The method according to claim 1 wherein the compound administered is levorphanol, cyclazocine, phenazocine, butorphanol, pentazocine or oxilorphan, or a nontoxic pharmaceutically acceptable acid addition salt thereof.
Claim 29
Dependent Claim
33 words
The method according to claim 27 wherein the compound is in the form of a long-chain carboxylic acid salt, the carboxylic acid portion of the salt containing from 10 to 20 carbon atoms.
Claim 30
Dependent Claim
18 words
The method according to claim 28 wherein the long-chain carboxylic acid salt is a stearate, palmitate or myristate.
Claim 31
Dependent Claim
74 words
A pharmaceutically acceptable nasal dosage form for eliciting an analgesic response in a warm-blooded animal, which comprises (i) an analgesically effective amount of morphine, hydromorphone, metopon, oxymorphone, desomorphine, dihydromorphine, levorphanol, cyclazocine, phenazocine, 3-hydroxy-N-methylmorphinan, levophenacylmorphan, metazocine, norlevorphanol, phenomorphan, nalorphine, nalbuphine, buprenorphine, butorphanol, levallorphan or pentazocine, or a nontoxic pharmaceutically acceptable acid addition salt thereof, and (ii) a nontoxic pharmaceutically acceptable nasal carrier therefor, said nasal dosage form comprising a nasal ointment or a nasal gel.
Claim 32
Dependent Claim
74 words
A pharmaceutically acceptable nasal dosage form for eliciting an analgesic response in a warm-blooded animal, which comprises (i) an analgesically effective amount of morphine, hydromorphone, metopon, oxymorphone, desomorphine, dihydromorphine, levorphanol, cyclazocine, phenazocine, 3-hydroxy-N-methylmorphinan, levophenacylmorphan, metazocine, norlevorphanol, phenomorphan, nalorphine, nalbuphine, buprenorphine, butorphanol, levallorphan or pentazocine, or a nontoxic pharmaceutically acceptable acid addition salt thereof, and (ii) a nontoxic pharmaceutically acceptable nasal carrier therefor, said nasal dosage form comprising a nasal ointment or a nasal gel.
Claim 33
Dependent Claim
14 words
A dosage form according to claim 30, said dosage form comprising a nasal ointment.
Claim 34
Dependent Claim
14 words
A dosage form according to claim 30, said dosage form comprising a nasal gel.
Claim 35
Dependent Claim
16 words
A dosage form according to claim 32, said dosage form comprising a sustained release nasal gel.
Claim 36
Dependent Claim
31 words
A dosage form according to claim 30, wherein (i) comprises an analgesically effective amount of morphine or buprenorphine, or of a nontoxic pharmaceutically acceptable acid addition salt of morphine or buprenorphine.
Claim 37
Dependent Claim
36 words
A dosage form according to claim 30, wherein the compound administered is in the form of a long chain carboxylic acid salt, the carboxylic acid portion of the salt containing from 10 to 20 carbon atoms.
Claim 38
Dependent Claim
71 words
A pharmaceutically acceptable nasal dosage form for eliciting a narcotic antagonist response in a warm-blooded animal, which comprises (i) a narcotic antagonist effective amount of naloxone, naltrexone, diprenorphine, nalmexone, cyprenorphine, levallorphan, alazocine, oxilorphan, cyclorphan, nalorphine, nalbuphine, buprenorphine, butorphanol, cyclazocine or pentazocine, or a nontoxic pharmaceutically acceptable acid addition salt thereof, and (ii) a nontoxic pharmaceutically acceptable nasal carrier therefor, said nasal dosage form comprising a nasal ointment or a nasal gel.
Claim 39
Dependent Claim
71 words
A pharmaceutically acceptable nasal dosage form for eliciting a narcotic antagonist response in a warm-blooded animal, which comprises (i) a narcotic antagonist effective amount of naloxone, naltrexone, diprenorphine, nalmexone, cyprenorphine, levallorphan, alazocine, oxilorphan, cyclorphan, nalorphine, nalbuphine, buprenorphine, butorphanol, cyclazocine or pentazocine, or a nontoxic pharmaceutically acceptable acid addition salt thereof, and (ii) a nontoxic pharmaceutically acceptable nasal carrier therefor, said nasal dosage form comprising a nasal ointment or a nasal gel.
Claim 40
Dependent Claim
14 words
A dosage form according to claim 36, said dosage form comprising a nasal ointment.
Claim 41
Dependent Claim
14 words
A dosage form according to claim 36, said dosage form comprising a nasal gel.
Claim 42
Dependent Claim
16 words
A dosage form according to claim 38, said dosage form comprising a sustained release nasal gel.
Claim 43
Dependent Claim
38 words
A dosage form according to claim 36, wherein (i) comprises a narcotic antagonist effective amount of naloxone, naltrexone, nalorphine, nalbuphine or buprenorphine, or of a nontoxic pharmaceutically acceptable acid addition salt of naloxone, naltrexone, nalorphine, nalbuphine or buprenorphine.
Claim 44
Dependent Claim
36 words
A dosage form according to claim 36, wherein the compound administered is in the form of a long chain carboxylic acid salt, the carboxylic acid portion of the salt containing from 10 to 20 carbon atoms.
Claim 45
Dependent Claim
74 words
A pharmaceutically acceptable sustained release nasal dosage form for nasally delivering systemic therapeutic levels of drug to a warm-blooded animal which comprises (i) a systemically therapeutically effective amount of a long chain carboxylic acid salt of morphine, hydromorphone, metopon, oxymorphone, desomorphine, dihydromorphine, levorphanol, cyclazocine, phenazocine, 3-hydroxy-N-methylmorphinan, levophenacylmorphan, metazocine, norlevorphanol, phenomorphan, nalorphine, nalbuphine, buprenorphine, butorphanol, pentazocine, naloxone, naltrexone, diprenorphine, nalmexone, cyprenorphine, levallorphan, alazocine, oxilorphan or cyclorphan, and (ii) a nontoxic pharmaceutically acceptable nasal carrier therefor.
Claim 46
Dependent Claim
74 words
A pharmaceutically acceptable sustained release nasal dosage form for nasally delivering systemic therapeutic levels of drug to a warm-blooded animal which comprises (i) a systemically therapeutically effective amount of a long chain carboxylic acid salt of morphine, hydromorphone, metopon, oxymorphone, desomorphine, dihydromorphine, levorphanol, cyclazocine, phenazocine, 3-hydroxy-N-methylmorphinan, levophenacylmorphan, metazocine, norlevorphanol, phenomorphan, nalorphine, nalbuphine, buprenorphine, butorphanol, pentazocine, naloxone, naltrexone, diprenorphine, nalmexone, cyprenorphine, levallorphan, alazocine, oxilorphan or cyclorphan, and (ii) a nontoxic pharmaceutically acceptable nasal carrier therefor.
Claim 47
Dependent Claim
29 words
A dosage form according to claim 42, wherein (i) comprises a systemically therapeutically effective amount of a long chain carboxylic acid salt of naloxone, naltrexone, nalorphine, nalbuphine or buprenorphine.
Claim 48
Dependent Claim
21 words
A dosage form according to claim 42, wherein the carboxylic acid portion of said salt contains 10 to 20 carbon atoms.
Claim 49
Dependent Claim
16 words
A dosage form according to claim 44, wherein said salt is a stearate, palmitate or myristate.
Claim 50
Dependent Claim
21 words
A dosage form according to claim 42, said dosage form comprising a nasal solution, nasal suspension, nasal ointment or nasal gel.
Claim 51
Dependent Claim
30 words
A dosage form according to claim 42, wherein (i) comprises a systemically therapeutically effective amount of a long chain carboxylic acid salt of levorphanol, cyclazocine, phenazocine, butorphanol, pentazocine or oxilorphan.
Claim 52
Dependent Claim
34 words
A method for eliciting an analgesic response in a warm-blooded animal, which comprises nasally administering to said animal an analgesically effective amount of a pharmaceutically acceptable nasal dosage form as claimed in claim 30.
Claim 53
Dependent Claim
36 words
A method for eliciting a narcotic antagonist response in a warm-blooded animal, which comprises nasally administering to said animal a narcotic antagonist effective amount of a pharmaceutically acceptable nasal dosage form as claimed in claim 36.
Claim 54
Dependent Claim
36 words
A dosage form according to claim 36, wherein (i) comprises a narcotic antagonist effective amount of butorphanol, pentazocine, cyclazocine or oxilorphan, or of a nontoxic pharmaceutically acceptable acid addition salt of butorphanol, pentazocine, cyclazocine or oxilorphan.
Claim 55
Dependent Claim
37 words
A dosage form according to claim 30, wherein (i) comprises an analgesically effective amount of levorphanol, cyclazocine, phenazocine, butorphanol or pentazocine, or of a nontoxic pharmaceutically acceptable acid addition salt of levorphanol, cyclazocine, phenazocine, butorphanol or pentazocine.
References Cited (Backward Citations)
US4275059A
Cited
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| 7.5 Years (Year 8) | 1991-08-07 | 1992-02-06 | 1992-08-07 | $3760.00 | Window Closed / Lapsed |
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