Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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Patent Application
for
METHOD FOR PREVENTING OR MINIMIZING
BIODEGRADATION OF A SUBSTANCE
Background of the Invention
This invention relates to the extension of the useful
lifetimes of biodegradable products by substituting lesser
biodegradable ingredients having the same required
functional characteristics such as odor. The practice of
the invention relates to identifying such lesser
biodegradable substances and substituting them, in
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existing or planned products, for those substances more
subject to degradation.
Many substances lose functional lifetimes ?oecause of
their vulnerability to microbial degradation. In a number
of instances, substances with lesser biodegradability are
substituted, such as polyvinyl for canvas, or fiberglass
for wood. In these instances, the knowledge of the
resistance of the selected substance to microbial decay is
a factor in guiding the selection. Even though the
immediate cost of the substitute is higher, the reduced
biodegradability makes the substitution economical over
the lifecycle of the product. There are, however, many
instances in which there is no knowledge of longer lasting
substitutes. These include instances in which other,
perhaps initially more expensive, substances offer the
same required functionality, but their greater resistance
to biodegradation is unknown, as is, hence, their possible
overall economic benefit. In other instances, in which
unnatural optical isomers, stereoisomers, constitutional
isomers, or other forms of the substances exist, useful
lifetimes of the products can be extended by virtue of the
relative nonbiodegradability of the unnatural or less
common forms or substances. Lesser biodegradability is
conferred by the fact that biodegrading bacteria, not
having had long exposure to these substances, have not
evolved the capability to metabolize them.
One aspect of this invention relates to a method for
preventing or minimizing biodegradation of a substance
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which normally contains a naturally occurring optical
isomer (or enantiomer, or optical stereoisomer). More
particularly, this aspect of the invention relates to a
process for rendering a fragrant substance, or surface,
either bearing microorganisms or subject to deliberate or
accidental contamination with microorganisms,
odoriferous, e.g., fragrant, for an extended period of
time.
Next to sight, the sense of smell is reported to be
that sense most widely appreciated. It plays an
important role in our everyday lives. For this reason,
the fragrance industry has grown to its present enormous
size. Commercially sold fragrances are based on natural
products and synthetic ones. The latter have become of
increasing importance as the science of chemistry has
become more inventive. Natural fragrances have also been
synthesized. However, many of the most pleasant, or
otherwise desired odors are highly transient, requiring
frequent re-applications, or disappearing after periods
shorter than desired for the intended uses.
Fragrant or odoriferous preparations generally
consist of two functional components: the odor-producing
compound or material, and a vehicle which serves as a
carrier for the fragrant molecules. Such vehicles have
served their purpose when the fragrance has been
adequately disseminated. These vehicles are generally
short-chain organic compounds which then evaporate quite
quickly. This leaves the generally longer-chain fragrant
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molecules in situ in the desired locations from which
they, in turn, volatilize, although somewhat more slowly.
The sustained volatilization of these fragrant molecules
achieves the desired effect by contacting the olfactories
of the target persons or animals in the affected area.
While the fragrant compound applied to the site will
ultimately be completely exhausted through
volatilization, the full potential of this effective time
is seldom, if ever, realized. This is because many
fragrant molecules are biodegradable and they are
generally applied to areas rich in microorganisms. An
application is to skin, which is well known to be heavily
laden with microorganisms. However, all other common
surfaces are also heavily populated with microorganisms.
The interests of economy and personal appearance require
that perfumes, for example, be applied sparingly. The
biodegradability of the organic fragrance molecules
results in the microbial populations attacking these
molecules, metabolizing them and rendering the remains
non-fragrant, less fragrant, or even of an undesirable
odor. The otherwise expected useful time of the
application of the product is thus effectively reduced.
In recent years, there has been a continuing
replacement of natural fragrances with chemically
synthesized molecules. Some are identical to natural
fragrances, but are made synthetically more cheaply than
can otherwise be obtained. Others are novel compounds,
but these are also generally biodegradable. Both types
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of products suffer the same fate as described above for
the natural fragrances.
Summary Of The Invention
In the broadest aspect of this invention, there is
provided a method for preventing or minimizing
biodegradation of a substance which normally contains a
biodegradable compound, which process comprises replacing
the biodegradable compound with a corresponding lesser
biodegradable compound providing the same desired
functionality.
In accordance with one aspect of this invention,
there is provided a method for preventing or minimizing
biodegradation of a substance which normally contains a
naturally occurring optical isomer, which process
comprises replacing the naturally occurring optical
isomer with the corresponding unnatural optical isomer.
Examples of such substances include fragrances,
substances which contain fragrances, and nonfragrant
substances which contain optical isomer(s), such as body
lotions, soaps, deodorants, and dyes and paints.
In a preferred embodiment of this invention, there
is provided a process for prolonging emanation of odors)
from a substance or surface containing one or more
odoriferous optically isomeric compounds and which
substance or surface also contains or becomes
contaminated with microorganisms, which process comprises
selecting (an) unnatural optical isomers) of the
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compounds) to prevent or delay biodegradation of the
odoriferous compound(s).
More generally, it has now been found that a
functional substance or compound may retain the desired
function for an extended period of time by substituting
its non-naturally occurring optical stereoisomer, or an
uncommon isomer or lesser biodegradable substance
possessing the same functionality. The resulting
substance will remain functional for a longer period of
time than if the more naturally occurring form or the
naturally occurring uncommon form or substance had been
applied. This is because the non-naturally occurring
form or the naturally occurring uncommon form or
substance is non-biodegradable, or is of greatly reduced
biodegradability since the microbial enzymes necessary to
the biodegradation process can cope only with the more
commonly occurring form or substance.
Detailed Description Of The Invention
Some of the organic molecules synthesized for
fragrance purposes, and some of the natural fragrance
molecules which can be synthesized have structures which
contain carbon atoms bonded to four different atomic
groups. The four atomic groups can assume one of two
opposite configurations about their central carbon atom.
For the purpose of chemical reactions, these
configurations behave identically. Although little used
as fragrances, amino acids and carbohydrates are
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important examples of chirality, the occurrence of
optical stereoisomers of the same molecule, and serve to
illustrate the point. Virtually all amino acids in
nature are of the optically stereoisomeric form
designated "left handed", while natural carbohydrates
occur almost exclusively in the optically stereoisomeric
form called "right handed". (These common designations
derive from their mirror images which demonstrate the
chemical identity, and non-superimposability of the two
forms of the same molecule.) The reason for the natural
preference of one optical stereoisomer over its opposite
form is unknown, but all known life forms follow this
preference in their consumption and production of chiral
organic compounds.
Some natural chemicals used in perfumery, and which
have optical isomers, are listed in Table 1.
Table 1. Some Fragrances and their optical Isomers
NATURAL OPTICAL ISOMER UNNATURAL OR LESS COMMON
NATURAL OPTICAL ISOMER
(1R, 2S, 5R) - (-) -Menthol (1S, 2R, 5S) - (+) -Menthol
(R)-(+)-Citronellal (S)-(-)-Citronellal
(+)-Limonene (-)-Limonene
(-)-Menthone Three stereoisomers
(1R)-(-)-Menthyl Acetate (1S)-(+)-Menthyl Acetate
The strong preference, or specificity, for natural
optical isomers displayed by biological entities is
because virtually all biological reactions are conducted
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through the participation of enzymes. From the time life
originated, its first enzymes have consistently passed on
their optical isomeric specificity to all life forms
evolved down through the eons. Enzymes, being templates
which position molecules for specific reactions, do
distinguish between optical isomers of the same molecule.
Not being able to fit physically to the other optical
isomer of the reactive molecular species, an enzyme
cannot induce the reaction with the unnatural optical
isomer.
The sense of smell has been attributed to enzymatic
reactions: "Olfactory transduction begins with the
binding of an odorant ligand to a protein receptor of the
olfactory neuron cell surface, initiating a cascade of
enzymatic reactions... "(Breer, H., Semin. Cell Bio1 5,
25, 1994; Sheppard, G.M., Neuron 13, 771, 1994, cited by
Zhao, H. et a1, Science, 279, 237, 1998). A fundamental
characteristic of enzymatic reactions is their
specificity for the molecule they catalyze into reaction.
"Perhaps the most striking aspect of the specificity of
enzymes is their ability to select between
enantiomorphous compounds. This may be termed
stereochemical specificity. For example,
carboxypeptidase, which catalyzes the hydrolysis of
carbobenzoxyglycyl-L-phenalalanine, has no measurable
action on carbobenzoxyglycyl-D-phenalalanine. ...These
examples of stereochemical specificity involve an
absolute discrimination between enantiomorphs." (General
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Biochemistry, Fruton and Simmonds, eds, 3rd printing, p.
277, John Wiley & Sons, Inc., NY, 1960). A number of
fragrant or odoriferous compounds are natural optical
isomers. It would be expected that the unnatural
enantiomers of these compounds would not trigger the
sense of smell, because their molecules would not fit the
protein (enzyme) receptor encountered. Since the enzyme
receptors have evolved to fit with natural products only,
the unnatural optical isomer would not fit, and,
therefore, no odor-sensing reaction would be expected to
occur with the neuron. However, the inventors have found
that both the naturally occurring optical stereoisomer
and the non-naturally occurring optical stereoisomer have
the same odor, which demonstrates the core of this
invention.
The odoriferous compounds used in the practice of
the fragrance-prolonging aspect of this invention may be
used in perfumes, eau de colognes, powders, mouth washes,
dentifrices, confections, deodorants for personal and
area uses, douches, hair applications, simulated odors
for various products (such as leather odors for plastic
upholstery), tobacco products, insect and animal
repellants and attractants, and the wide variety of other
products and uses for fragrances, masking odors,
artificial odors, or other scents including those used in
foodstuffs, beverages and the like.
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EXAMPLE 1 - Menthol as a Fragrance
The naturally-occurring optical isomer of menthol
(1R,2S,5R)-(-) is used as a fragrance in a variety of
products, such as perfumes, gums, and cigarettes. Both
the natural and the unnatural (1S,2R,5S)-(+) optical
isomer of menthol were obtained in 99o purity. A O.OO1M
solution of each enantiomer was prepared in reagent grade
acetone. The solutions were allowed to equilibrate at
room temperature for approximately one hour. Twenty
drops of each solution were pipetted into separate glass
Petri dishes. All glassware was clean. The acetone was
then allowed to evaporate at room temperature. Human
subjects then smelled the two Petri dishes separately and
recorded any sensations. The subjects had been
instructed to determine the presence of odor in the Petri
dishes, and, if odor emanated from each, to determine
whether the odors were the same or different. The test
was performed twice on each of six human subjects, three
female and three male. Each subject was given freshly
prepared Petri dish servings to smell, and each
immediately recorded his or her impressions without
communicating with the other subjects.
All six subjects found that the unnatural form of
menthol had odor. Moreover, all six found the odor of
the unnatural form to be the same as that of the natural
form. These results constitute evidence that the sense
of smell is not enzymatic as heretofore believed by the
scientific community. This unexpected finding
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constitutes the essential basis of the innovation claimed
herein.
EXAMPLE 2 - Odor Absorber/Deodorant
Objectionable odors may be absorbed by a variety of
chemicals. Such chemicals may be added to an odoriferous
material, or sprayed onto surfaces. This example relates
to the use of zinc glutamate as an odor absorber. Zinc
glutamate is normally used in the form of zinc salt of L-
glutamic acid for this purpose. However, this form of
the compound is readily biodegraded by microorganisms
that are generally abundant in the treatment area. In
this embodiment of the invention, the zinc salt of D-
glutamic acid is substituted for the normal form, with
the result that the odor-absorbing material, and, hence,
odor removal function, lasts considerably longer than
when the natural form of zinc glutamate is used.
Other chemicals with the deodorant function include
zinc gluconate and sodium aluminum chlorohydroxy lactate.
D-gluconic acid and D-lactic acid are natural products,
which are readily biodegradable. The use of their
unnatural optical isomers, the zinc salt of L-gluconic
acid and the sodium aluminum salt of L-lactic acid,
instead of the natural products will result in the odor
absorbing material lasting considerably longer.
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EXAMPLE 3 - Humectant
Besides their application in food, pharmaceutical
and other industries, D-glucitol (i.e., sorbitol) and D-
mannitol, the naturally occurring sugar alcohol, are
commonly used as humectants (water-attracting/binding) as
well as emollient ingredients in many cosmetic products,
for example, in body lotions and sunblock. A
moisturizing lotion, in which D-glucitol is provided as a
humectant and emollient, is applied to the skin daily or
twice daily, especially by persons with dry skin. The
lotion is spread over the skin, where it comes into
contact with the coating of microorganisms normally
covering the skin. These microorganisms quickly
biodegrade D-glucitol, reducing the length of time over
which the moisturizing product is effective, requiring
more frequent applications. In this example, L-glucitol,
the unnatural optical isomer, is used instead of D-
glucitol. The skin microorganisms cannot appreciably
biodegrade the L-glucitol, thereby permitting the
moisturizer product to remain effective for a longer
period of time.
In a related example, L-mannitol is used instead of
D-mannitol based on the same concept, and producing the
same result.
EXAMPLE 4 - Underarm Deodorant/Antiperspirant
Deodorants operate by absorbing odors, reducing
perspiration at the skin surface or masking malodors with
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other odors. Popular underarm deodorants consist of hard
gels in the forms of sticks or bars which are applied
under the arm where they leave a film of their material.
A paramount feature of such deodorants is the length of
time the application retains its effectiveness. The
underarm harbors many microorganisms which biodegrade the
organic ingredients of the deodorant, thereby
significantly reducing the lifetime of the product. A
widely used stick applicator deodorant/antiperspirant
contains cobalt acetylmethionate as its principal active
ingredient. Methionine is optically active. This
example of the invention substitutes the unnatural
optical isomer of methionine (D-methionine) for the
natural isomer (L-methionine), thereby extending the
lifetime of this key ingredient, and hence the
effectiveness of the product.
EXAMPLE 5 - Sunblock Lotion
Menthyl anthranilate is frequently used as the
active ingredient in sunblock lotions applied to the body
to prevent excessive sunburn by absorbing the ultraviolet
rays of the sun. This compound is prepared from menthol
by its esterification with anthranilic acid. The
enantomeric form of the menthol used is carried into the
product. Currently, the naturally occurring enantiomer
of menthol (1-menthol) is used, or, in the case of
synthetic menthol, the racemic mixture (1- and d-menthol
in equal quantities) produced by the synthesis is used.
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L-menthyl anthranilate, made from 1-menthol, is
biodegradable. Skin bacteria biodegrade the 1-menthyl
anthranilate, significantly shortening the lifetime of
the sunblock lotion. In this example, the unnatural
enantiomer of menthol (d-menthol) is used to make the
menthyl anthranilate used in the sunblock lotion. Being
lesser biodegradable, the d-menthyl anthranilate provides
the sunblock lotion with a longer useful lifetime than
does the normally used 1- or dl-menthyl anthranilate.
EXAMPLE 6 - Substitution of Lesser
Biodegradable Compound with Same Functionality
This example illustrates the broad application of
this invention beyond the concept of using a lesser
biodegradable isomer of a compound. In this case, a
completely different compound, but with the same
functionality and with lesser biodegradability, is
substituted for the normally used compound. A widely
used stick deodorant has aluminum zirconium
tetrachlorohydrex glycine as its active ingredient. This
compound is biodegradable. However, since glycine is not
optically active, there is no enantiomeric, lesser
biodegradable form of that amino acid to substitute for
it. However, the function of the glycine is to
neutralize the active ingredient in order to prevent or
reduce its irritability to the skin of the user. Another
amino acid, in this case alanine, will serve the same
function if used in place of glycine. Alanine does have
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optical isomers L-alanine and D-alanine. According to
the teachings of this invention, the lesser biodegradable
enantiomer of alanine (D-alanine) is used to make
aluminum zirconium tetrachlorohydrex alanine. This
compound provides the deodorant product with the same
functionality as did the aluminum zirconium
tetrachlorohydrex glycine, but being less biodegradable,
provides longer useful life for the product.
