US2009028968A1PendingUtilityA1
Pharmaceutical Platform Technology for the Development of Natural Products
Est. expiryMar 30, 2027(~0.7 yrs left)· nominal 20-yr term from priority
A61K 36/48G16B 35/00G16C 20/60G16C 20/30G06F 18/211G01N 33/483G16C 20/64G16B 5/00
62
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Claims
Abstract
The present invention provides a set of in vitro and in silico methodologies for predicting in vivo pharmacokinetics and pharmacodynamics of multiple components; the methodologies comprise mathematical models for solving multiple unknowns which are linearly independent and/or interacting with each other. The present invention can be applied to develop phytomedicines which contain multiple active ingredients without prior identification, isolation and purification of these components.
Claims
exact text as granted — not AI-modified1 . A method of predicting in vivo pharmacokinetics and pharmacodynamics properties of a composition with multiple components, comprising the steps of:
a) determining parameters describing the rate of elimination of the components in a plurality of mammalian tissue systems; b) determining parameters describing distribution of the components in a plurality of mammalian tissue systems; and c) inputting the parameters into mathematical models that will generate outputs to predict the pharmacokinetics and pharmacodynamics properties of the composition in vivo.
2 . The method of claim 1 , further comprising the steps of determining parameters for active metabolites of the components according to steps (a) to (c), wherein outputs of the mathematical models will predict the pharmacokinetics and pharmacodynamics properties of the composition and the active metabolites in vivo.
3 . The method of claim 1 , wherein the pharmacokinetics and pharmacodynamics properties comprise concentration-time profiles and response-time profiles for the components.
4 . The method of claim 1 , wherein the parameters are obtained from in vitro or in vivo studies.
5 . The method of claim 1 , wherein the pharmacokinetics or pharmacodynamics properties of individual component are determined by in silico simulation.
6 . The method of claim 5 , wherein the in silico simulation determines pharmacokinetics or pharmacodynamics properties for the components present in minute amount in the composition.
7 . The method of claim 1 , wherein the pharmacokinetics and pharmacodynamics properties comprise determining the potency of an individual component, and synergism or inhibition among the components.
8 . The method of claim 7 , wherein determining the potency of an individual component comprises receptor binding assay, enzymatic assay, biochemical response assay, or assays with isolated tissues or organs.
9 . The method of claim 1 , wherein the mathematical models are capable of solving multiple unknowns that are linearly independent or interacting with each other.
10 . The method of claim 1 , wherein the mathematical models are selected from the group consisting of least absolute shrinkage and selection operator (LASSO), wavelet-based deconvolution, compressed sensing, and gradient projection algorithm.
11 . The method of claim 1 , wherein the mathematical models comprises
r
≈
r
_
+
∑
i
w
i
(
d
i
-
d
_
i
)
+
∑
i
w
i
′
(
d
i
-
d
_
i
)
2
+
∑
i
,
j
w
i
,
j
(
d
i
-
d
_
i
)
(
d
j
-
d
_
j
)
,
wherein r is linearized response, r is average linearized response; w i is weight of the i component (relates to potency), d i is the dose of component i and d i and d j are average dose of the i th and j th component, w i,j is the weight of the interacting pair.
12 . The method of claim 1 , wherein the mathematical models comprises
A
=
α
0
+
∑
i
=
1
n
α
i
x
i
+
∑
i
=
1
n
∑
j
=
1
n
β
i
,
j
x
i
x
j
,
wherein α 0 and α i are baseline activity and activity coefficient of component i respectively, x i and x j are components i and j respectively, β i,j is activity coefficient of interacting pair x i and x j , wherein said equation is able to predict an optimized composition to achieve maximum possible potency.
13 . The method of claim 1 , wherein the mammalian tissue systems are selected from the group consisting of gastrointestinal tract, liver, kidney, blood, mammary gland, uterus, prostate, brain, and bone.
14 . The method of claim 1 , wherein the rate of elimination comprises one or more parameters selected from the group consisting of rate of metabolism, rate of absorption, and rate of degradation.
15 . The method of claim 14 , wherein the rate of absorption is determined by rate of permeability measured using cultured cells or intestinal tissues.
16 . The method of claim 13 , wherein determining the rate of elimination in gastrointestinal tract comprises assays using artificial gastric or intestinal juice, intestinal flora or intestinal microsomes.
17 . The method of claim 13 , wherein determining the rate of elimination in liver comprises assays using freshly harvested hepatocytes, cryopreserved hepatocytes, hepatic microsomes, hepatic cytosol or S-9 fractions.
18 . The method of claim 13 , wherein determining the rate of elimination in kidneys comprises in silico simulation.
19 . The method of claim 13 , wherein determining distribution in blood comprises determining binding to plasma protein, binding to blood protein, pKa, log P, log D, and volume of distribution of a component.
20 . A composition comprising multiple components as identified by the method of claim 1 , wherein the components have desirable in vivo pharmacokinetics and pharmacodynamics properties as determined by the method of claim 1 .
21 . The composition of claim 20 , comprising Red clover ( Trifolium pratense ).
22 . The composition of claim 21 , wherein the Red clover composition comprises formononetin, biochanin A and their glycosides.Join the waitlist — get patent alerts
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