Hydroxysilyl-terminated polyoxyethylene compound, quaternary-sal

Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...

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424449, 514946, 514947, 556423, 556425, 528 14, 528 15, 528 21, 528 28, A61F 1302

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056246803

DESCRIPTION:

BRIEF SUMMARY
TECHNOLOGICAL FIELD

The present invention relates to a hydroxysilyl-terminated polyoxyethylene compound, of the following formula ##STR1## wherein, each of R.sup.1 and R.sup.2 which may be the same or different, is a C.sub.1-6 alkyl group or a phenyl group; A is an alkyl group or a group represented by --(CH.sub.2).sub.p --SiR.sup.1 R.sup.2 OH; p is an integer of from 2 to 6; an average value of degree of polymerization, m, is a real number of from 3 to 100, and a quaternary-salt-terminated polyoxyethylene/polyorganosiloxane block copolymer, of the following formula (II): ##STR2## wherein, each of R.sup.1 to R.sup.6 which may be the same or different, is a C.sub.1-6 alkyl group or a phenyl group; each of R.sup.7 to R.sup.9 which may be the same or different, is an alkyl group, a substituted alkyl group or a phenyl group, or two or three of R.sup.7 to R.sup.9 and the nitrogen atom connected thereto together may form a heterocycle containing a nitrogen; X.sup.- is a counter anion in the quaternary salt; Y is an alkyl group or a quaternary-salt-terminated polyorganosiloxane chain represented by the following formula (III): ##STR3## where p is an integer of from 2 to 6; q is an integer of from 1 to 6; an average value of degree of polymerization, m or n, is a real number of from 3 to 100; each of R.sup.3 and R.sup.4 may be the same or different in each of the repeating unit. The present invention also provides an agent for promoting percutaneous absorption of a drug, which comprises said quaternary-salt-terminated polyoxyethytene/polyorganosiloxane block copolymer.


BACKGROUND ART

Studies have been actively conducted on drug delivery systems (DDS) for the purpose of efficiently delivering drugs to desired sites and avoiding side effects. Among them, a percutaneous absorption system wherein the skin is the application site of a drug, has attracted an attention in recent years. The merit of this system include .vertline.=@ it is thereby possible to avoid the first-pass effect at the liver, .vertline.=A the percutaneous penetration rate of the drug can be controlled so that a long active constant drug level can be maintained, .vertline.=B the administration is not influenced by foods or vomiting, .vertline.=C the administration can easily be adjusted, and .vertline.=D the drug can be administered in the vicinity of the desired site. However, it still has drawbacks such that .vertline.=@ the application is limited to a drug, the dose of which is relatively small, .vertline.=A useful drugs are relatively limited, .vertline.=B there is a possibility that deterioration of the keratin layer or a skin allergy reaction is thereby promoted, and .vertline.=C no rapid action can be expected. Under these circumstances, a combined use of a percutaneous absorption-promoting agent is being studied to overcome such drawbacks.
For example, it has been pointed out in Journal of Controlled Release, Vol. 25, pp. 1-22 (1993) that a variety of low-molecular-weight compounds are effective as percutaneous absorption-promoting agents, with describing abstracts of patents with respect to dimethylsulfoxide, 1-alkylpyrrolidone derivatives, 1-dodecylazacycloheptan-2-on, and the like. The present inventors have proposed, as percutaneous absorption-promoting agents having low toxicity and irritation to the skin, polymeric compounds such as a polymer containing a benzalkonium salt in its side chain (Journal of Controlled Release, Vol. 13. pp.63-71 (1990)), a polymer containing a pyridinium salt in its side chain (Polymer, Vol. 32, No. 11, 2106-2111 (1991)), a polyorganosiloxane containing a N-methylpyridinium salt in its one terminal (Polymer, Vol. 33, No. 10, 2203-2207 (1992)), and a polyorganosiloxane containing a pyridinium or an ammonium salt in its one terminal (EP-0484857A, U.S. Pat. No. 5,200,488).
Among the above promoting agents, however, particularly low-molecular-weight compounds such as dimethylsulfoxide, 1-alkylpyrrolidone derivatives and 1-dodecylazacycloheptan-2-on, had problems at practical application in that they have a to

REFERENCES:
patent: 5087715 (1992-02-01), Snow
patent: 5200488 (1993-04-01), Nagase et al.

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