WO2000068369A1

WO2000068369A1 - Method for preventing or minimizing biodegradation of a substance

Info

Publication number: WO2000068369A1
Application number: PCT/US2000/008881
Authority: WO
Inventors: Gilbert Levin; Roy Pinchot; Yongming Lu
Original assignee: Biospherics Incorporated
Priority date: 1999-05-06
Filing date: 2000-04-04
Publication date: 2000-11-16
Also published as: EP1173558A4; EP1173558A1; CA2372612A1; AU4068400A; JP2003519246A

Abstract

There is disclosed a method for preventing or minimizing biodegradation of a substance which normally contains a biodegradable compound which comprises replacing the compound with a corresponding lesser biodegradable compound providing the same desired functionality.

Description

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 existing or planned products, for those substances more subject to degradation.

Many substances lose functional lifetimes because 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 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 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 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 odor(s) 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 isomer (s) of the compound (s) 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 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 (IS) - (+) -Menthyl Acetate

The strong preference, or specificity, for natural optical isomers displayed by biological entities is because virtually all biological reactions are conducted 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 Biol 5, 25, 1994; Sheppard, G.M. , Neuron 13, 771, 1994, cited by Zhao, H. et al , 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 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. 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 (IS, 2R, 5S) - (+) optical isomer of menthol were obtained in 99% purity. A 0.001M 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 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. 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 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. L-menthyl anthranilate, made from 1-menthol, is biodegradable. Skin bacteria biodegrade the l-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 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.

Claims

WHAT IS CLAIMED IS:

1. A method for preventing or minimizing biodegradation of a substance which normally contains a biodegradable compound which comprises replacing the compound with a corresponding lesser biodegradable compound providing the same desired functionality.

2. A method according to claim 1 wherein said compound is an odor absorber and/or a deodorant.

3. A method according to claim 2 wherein the zinc salt of L-glutamic acid is replaced with the zinc salt of D-glutamic acid.

4. A method according to claim 2 wherein the zinc salt of D-gluconic acid is replaced with the zinc salt of L-gluconic acid.

5. A method according to claim 2 wherein the sodium aluminum salt of D-lactic acid is replaced with the sodium aluminum salt of L-lactic acid.

6. A method according to claim 1 wherein said compound is a humectant .

7. A method according to claim 6 wherein D- glucitol is replaced with L-glucitol .

8. A method according to claim 6 wherein D- mannitol is replaced with L-mannitol.

9. A method according to claim 1 wherein said compound is an underarm deodorant and/or antiperspirant .

10. A method according to claim 9 wherein cobalt acetylmethionate (L-methionine) is replaced with cobalt acetylmethionate (D-methionine) .

11. A method according to claim 9 wherein aluminum zirconium tetrachlorohydrex glycine is replaced with aluminum zirconium tetrachlorohydrex complex with any unnatural amino acid (D-amino acid), such as D-alanine.

12. A method according to claim 1 wherein said compound is a sun block agent.

13. A method according to claim 12 wherein 1- or dl-menthyl anthranilate is replaced with d-menthyl anthranilate .

14. A method according to claim 1 wherein the compound being replaced is replaced with a lesser biodegradable compound which is not an isomer of the biodegradable compound which is being replaced.

15. A method according to claim 14 wherein aluminum zirconium tetrachlorohydrex glycine in a deodorant is replaced with aluminum zirconium tetrachlorohydrex D- alanine .

16. A method for preventing or minimizing biodegradation of a substance which normally contains a naturally occurring optical isomer which comprises replacing the naturally occurring optical isomer with the corresponding unnatural optical isomer.

17. A process for prolonging emanation of odor from a substance or surface containing one or more odoriferous optically isomeric compounds which process comprises selecting an unnatural optical isomer of the compound (s) for use in or on the substance or surface to prevent or delay biodegradation of the fragrance by microorganisms present on, or accidentally or deliberately contacting the substance or surface .

18. A process for rendering a substance or surface odoriferous for an extended period of time which comprises selecting an odoriferous compound which can exist in the form of optical stereoisomers, one being naturally occurring and the other being non-naturally occurring and applying to said substance or surface said non-naturally occurring optical stereoisomer to prevent or delay biodegradation of the odoriferous compound.

19. A process according to claim 18 wherein said surface is human skin, hair or mucosal tissue.

20. A process according to claim 18 wherein said odoriferous compound is a fragrance.

21. A process according to claim 18 in which the substance incorporating the odoriferous compound are selected from the group consisting of perfumes, eau de colognes, powders, mouth washes, dentrifices, confections, deodorants for personal and area uses, incenses, candles, shaving creams and lotions, body lotions, shampoos, laundry and dry cleaning products, dish cleansers, furniture and leather treatments, douches, hair applications, simulated odors for various products (such as leather odors for plastic upholstery) , tobacco products, household and personal cleansers, insect and animal repellents and attractants, foodstuffs, and alcoholic and non-alcoholic beverages.

22. A process according to claim 18 wherein said odoriferous compound is (IS, 2R, 5S) -(+) -menthol .

23. A process according to claim 18 wherein said odoriferous compound is (S) -(-) -citronellal .

24. A process according to claim 18 wherein said odoriferous compound is (+) -linalool .

25. A process according to claim 18 wherein said odoriferous compound is (IS) -(+) -methyl acetate.

26. An odoriferous product obtained by the process of claim 17.

27. An odoriferous product obtained by the process of claim 18.

28. An odoriferous product obtained by the process of claim 19.

29. An odoriferous product obtained by the process of claim 20.

30. An odoriferous product obtained by the process of claim 21.

31. An odoriferous product obtained by the process of claim 22.

32. An odoriferous product obtained by the process of claim 23.

33. An odoriferous product obtained by the process of claim 24.

34. An odoriferous product obtained by the process of claim 25.