US2009155235A1PendingUtilityA1
Aggregates with increased deformability, comprising at least three amphipats, for improved transport through semi-permeable barriers and for the non-invasive drug application in vivo, especially through the skin
Est. expiryOct 11, 2022(expired)· nominal 20-yr term from priority
A61K 47/10A61K 31/405A61K 47/16A61K 47/20A61P 29/00A61K 9/127A61K 9/1272A61K 47/12A61K 47/26A61K 31/196A61K 31/5415A61K 47/34A61K 31/192
73
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Claims
Abstract
The invention describes combinations of at least three amphipatic substances forming aggregate suspensions in a polar liquid. Judicious choice of system components, which differ at least 2-times to 10-times in solubility, ensures said aggregates to have extended, unusually adaptable surfaces. This is probably due to simultaneous action on said aggregates of at least two more soluble substances amongst said three system components, at least one of which is an active ingredient and preferably a drug; the third component alternatively, can take the role of a drug. The patent further deals with the use of said combinations in pharmaceutical preparations capable of transporting drugs into the body of warm blood creatures. This is made possible by the drug loading capability of said aggregates with the highly flexible and deformable coating, which renders the resulting drug carriers highly adaptable. The patent finally reveals suitable methods and favourable conditions for carrier manufacturing and application.
Claims
exact text as granted — not AI-modified1 - 92 . (canceled)
93 . A method for selecting a vesicular composition that is capable of delivering an active agent through a barrier having pores, comprising:
a) determining the barrier transport resistance (p*) of a vesicular composition according to the following equation:
P
(
p
)
=
p
max
·
{
1
-
erf
(
p
*
p
)
+
4
p
*
π
p
·
exp
[
-
p
*
p
]
}
wherein
P(p) is the barrier penetrability as a function of transport driving pressure;
p is the transport driving pressure; and
p max is the maximum possible penetrability of the barrier,
the vesicular composition comprising:
(i) vesicles comprising:
(1) a lipid;
(2) a surfactant; and
(3) an active agent; and
(ii) a pharmaceutically acceptable liquid medium; and
b) selecting the vesicular composition if p* is higher than 50%.
94 . The method of claim 93 , wherein the vesicular composition that is selected has a p* that is between 50% and 60%.
95 . The method of claim 94 , wherein the vesicular composition that is selected has a p* that is 57%.
96 . The method of claim 93 , wherein the lipid is a glyceride, glycolipid, glycerophospholipid, isoprenoidlipid, sphingolipid, steroid, sterine, sterol, sulphur-containing lipid, lipid containing at least one carbohydrate residue, or polar fatty acid derivative.
97 . The method of claim 93 , wherein the lipid is a phosphatidylcholine, phosphatidyl-ethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidic acid, phosphatidylserine, sphingomyelin, sphingophospholipid, glycosphingolipids, cerebroside, ceramidpolyhexoside, sulphatide, sphingoplasmalogene, or ganglioside.
98 . The method of claim 93 , wherein the lipid is a phospholipid.
99 . The method of claim 98 , wherein the phospholipid is a phosphatidylcholine.
100 . The method of claim 99 , wherein the phosphatidylcholine is from soy-bean, or the phosphatidylcholine is egg lecithin.
101 . The method of claim 93 , wherein the surfactant is a non-ionic, zwitterionic, anionic, or cationic surfactant.
102 . The method of claim 93 , wherein the surfactant is a non-ionic surfactant.
103 . The method of claim 102 , wherein the non-ionic surfactant is a polyethyleneglycol-sorbitan-10 to 24 carbon atom fatty chain ester.
104 . The method of claim 103 , wherein the polyethyleneglycol-sorbitan-10 to 24 carbon atom fatty chain ester is a polyethyleneglycol-sorbitan-monolaurate or a polyethyleneglycol-sorbitan-monooleate.
105 . The method of claim 102 , wherein the non-ionic surfactant is a polyhydroxyethylene-10 to 24 carbon atom fatty chain ether.
106 . The method of claim 105 , wherein the polyethyleneglycol-10 to 24 carbon atom fatty chain ether is a polyhydroxyethylene-lauryl ether, a polyhydroxyethylene-myristoyl ether, or a polyhydroxyethylene-oleoyl ether.
107 . The method of claim 93 , wherein the lipid is a phophatidylcholine and the surfactant is a non-ionic surfactant.
108 . The method of claim 107 , wherein the non-ionic surfactant is present in an amount of about 2.5 mol % to 10 mol % of the amount of the phosphatidylcholine.
109 . The method of claim 93 , wherein the active agent is a cosmetic agent.
110 . The method of claim 93 , wherein the active agent is a drug.
111 . The method of claim 110 , wherein the drug is one or more of an adrenocorticostatic, β-adrenolytic, androgen, antiandrogen, antiparasitic, anabolic, anesthetic, analgesic, analeptic, antiallergic, antiarrhythmic, antiarterosclerotic, antiasthmatic, bronchospasmolytic, antibiotic, antidrepressive, antipsychotic, antidiabetic, antidote, antiemetic, antiepileptic, antifibrinolytic, anticonvulsive, anticholinergic, enzyme or corresponding inhibitor, coenzyme or corresponding inhibitor, antihistaminic, antihypertonic, biological inhibitor of drug activity, antihypotonic, anticoagulant, antimycotic, antimyasthenic, agent against Morbus Parkinson or Morbus Alzheimer, antiphlogistic, antipyretic, antirheumatic, antiseptic, respiratory analeptic, respiratory stimulant, broncholytic, cardiotonic, chemotherapeutic, coronary dilatator, cytostatic, diuretic, ganglium-blocker, glucocorticoid, anti-influenza agent, haemostatic, hypnotic, immunoglobulin or fragment thereof, immunologically active substance, bioactive carbohydrate, bioactive carbohydrate derivative, contraceptive, anti-migraine agent, mineralo-corticoid, morphine-antagonist, muscle relaxant, narcotic, neurotherapeutic, neuroleptic, neurotransmitter or antagonist thereof, small peptide, small peptide derivative, ophthalmic, sympathicomimetic, sympathicolytic, para-sympathicomimetic, para-sympathicolytic, psoriasis drug, neurodermitis drug, mydriatic, psychostimulant, rhinologic, sleep-inducing agent or antagonist thereof, sedating agent, spasmolytic, tuberculostatic, urologic agent, vasoconstrictor, vasodilatator, virustatic, growth factor, immunomodulator, recognition molecule, anticholinergic, antihistaminic, antihypertonic, anticoagulant, antimycotic, antimyasthenic, antiphlogistic, antipyretic, antirheumatic, antiseptic, broncholytic, cardiotonic, cytostatic, diuretic, haemostatic, mineralocorticoid, or wound-healing substance.
112 . The method of claim 111 , wherein the drug is an anesthetic.
113 . A method for transporting an active agent into and/or across mammalian skin, comprising applying to the skin a vesicular composition selected according to the method of claim 93 .
114 . A vesicular composition selected according to the method of claim 93 .
115 . A method for transporting an anesthetic agent into and/or across mammalian skin, comprising applying to the skin a vesicular composition comprising:
(a) vesicles comprising:
(i) a phosphatidylcholine;
(ii) a non-ionic surfactant; and
(iii) an anaesthetic agent that is in the form of a salt;
wherein the non-ionic surfactant is present in an amount of about 2.5 mol % to 10 mol % of the amount of the phosphatidyl choline; and
(b) a pharmaceutically acceptable, polar liquid medium,
wherein the barrier transport resistance (p*) of the vesicular composition according to the following equation:
P
(
p
)
=
p
max
·
{
1
-
erf
(
p
*
p
)
+
4
p
*
π
p
·
exp
[
-
p
*
p
]
}
is higher than 50%,
wherein
P(p) is the barrier penetrability as a function of transport driving pressure;
p is the transport driving pressure; and
p max is the maximum possible penetrability of the barrier.
116 . The method of claim 115 , wherein the vesicular composition has a p* that is between 50% and 60%.
117 . The method of claim 116 , wherein the vesicular composition has a p* that is 57%.
118 . The method of claim 115 , wherein the phosphatidylcholine is from soy-bean, or the phosphatidylcholine is egg lecithin.
119 . The method of claim 115 , wherein the non-ionic surfactant is a polyethyleneglycol-sorbitan-10 to 24 carbon atom fatty chain ester.
120 . The method of claim 119 , wherein the polyethyleneglycol-sorbitan-10 to 24 carbon atom fatty chain ester is a polyethyleneglycol-sorbitan-monolaurate or a polyethyleneglycol-sorbitan-monooleate.
121 . The method of claim 115 , wherein the non-ionic surfactant is a polyhydroxyethylene-10 to 24 carbon atom fatty chain ether.
122 . The method of claim 121 , wherein the polyethyleneglycol-10 to 24 carbon atom fatty chain ether is a polyhydroxyethylene-lauryl ether, a polyhydroxyethylene-myristoyl ether, or a polyhydroxyethylene-oleoyl ether.
123 . The method of claim 115 , wherein the anesthetic agent is morphine, hydromorphone, oxymorphone, oxycodone, buprenorphine, nalbuphine, pentazocine, cyclazocine, pethidine, methadone, dipipanone, dextromoramide, tramadol, dimethylthiambutene, procaine, chloroprocaine, hydroxyprocaine, propoxycaine, oxy-buprocaine, propoxymetacatine, piridocaine, leucinocaine, butacaine, tetracaine, hydroxytetracaine, -cetacaine, piperocaine, cyclomethycaine, parethoxycaine, stadacain, cinchocaine, lidocaine, pyrrocaine, ranocaine, butanilicaine, tolycaine, mepivacaine, bupivacaine, prilocaine, carticaine, propitocaine, dyclonine, pramocaine, fomocaine, quinisocaine, profenamine, promethazine, periciazine, perphenazine, prochlorperazine, triflumpromazine, trifluoperazine, fluphenazine, clomipramine, trimipramine, chloroprothixene, doxepin, or a thiepin.Join the waitlist — get patent alerts
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