AU1854297A - Urogenital and intestinal disorder compositions comprising substance derived from plant species of the ericaceae family and a lactic acid bacteria growth factor - Google Patents
Urogenital and intestinal disorder compositions comprising substance derived from plant species of the ericaceae family and a lactic acid bacteria growth factorInfo
- Publication number
- AU1854297A AU1854297A AU18542/97A AU1854297A AU1854297A AU 1854297 A AU1854297 A AU 1854297A AU 18542/97 A AU18542/97 A AU 18542/97A AU 1854297 A AU1854297 A AU 1854297A AU 1854297 A AU1854297 A AU 1854297A
- Authority
- AU
- Australia
- Prior art keywords
- group
- mixtures
- compositions
- composition according
- growth factor
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims description 92
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 title claims description 54
- 235000014655 lactic acid Nutrition 0.000 title claims description 27
- 239000004310 lactic acid Substances 0.000 title claims description 27
- 239000003102 growth factor Substances 0.000 title claims description 25
- 241000894006 Bacteria Species 0.000 title claims description 24
- 241000196324 Embryophyta Species 0.000 title claims description 19
- 241000208421 Ericaceae Species 0.000 title claims description 17
- 208000025609 Urogenital disease Diseases 0.000 title claims description 8
- 208000028774 intestinal disease Diseases 0.000 title claims description 7
- 239000000126 substance Substances 0.000 title description 6
- 241000186660 Lactobacillus Species 0.000 claims description 24
- 239000000284 extract Substances 0.000 claims description 24
- 229940039696 lactobacillus Drugs 0.000 claims description 21
- 241000894007 species Species 0.000 claims description 18
- 241000186000 Bifidobacterium Species 0.000 claims description 15
- 229920001542 oligosaccharide Polymers 0.000 claims description 15
- 150000002482 oligosaccharides Chemical class 0.000 claims description 15
- 239000002775 capsule Substances 0.000 claims description 11
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical class OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 10
- 239000003826 tablet Substances 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 9
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- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims description 6
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- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 claims description 6
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 claims description 6
- 239000001888 Peptone Substances 0.000 claims description 6
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- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 claims description 6
- 235000019319 peptone Nutrition 0.000 claims description 6
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 5
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- DUKURNFHYQXCJG-UHFFFAOYSA-N Lewis A pentasaccharide Natural products OC1C(O)C(O)C(C)OC1OC1C(OC2C(C(O)C(O)C(CO)O2)O)C(NC(C)=O)C(OC2C(C(OC3C(OC(O)C(O)C3O)CO)OC(CO)C2O)O)OC1CO DUKURNFHYQXCJG-UHFFFAOYSA-N 0.000 claims description 5
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 5
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 claims description 5
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- AIHDCSAXVMAMJH-GFBKWZILSA-N levan Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@@H]1[C@@H](O)[C@H](O)[C@](CO)(CO[C@@H]2[C@H]([C@H](O)[C@@](O)(CO)O2)O)O1 AIHDCSAXVMAMJH-GFBKWZILSA-N 0.000 claims description 5
- HOVAGTYPODGVJG-VEIUFWFVSA-N methyl alpha-D-mannoside Chemical compound CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O HOVAGTYPODGVJG-VEIUFWFVSA-N 0.000 claims description 5
- 229950006780 n-acetylglucosamine Drugs 0.000 claims description 5
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- 229920002307 Dextran Polymers 0.000 claims description 3
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- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims description 3
- NGFMICBWJRZIBI-UHFFFAOYSA-N alpha-salicin Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=CC=C1CO NGFMICBWJRZIBI-UHFFFAOYSA-N 0.000 claims description 3
- 239000000730 antalgic agent Substances 0.000 claims description 3
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 claims description 3
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- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 3
- 235000020939 nutritional additive Nutrition 0.000 claims description 3
- NGFMICBWJRZIBI-UJPOAAIJSA-N salicin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC=CC=C1CO NGFMICBWJRZIBI-UJPOAAIJSA-N 0.000 claims description 3
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- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 claims description 3
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- 229960002898 threonine Drugs 0.000 description 1
- 229960001312 tiaprofenic acid Drugs 0.000 description 1
- 235000015193 tomato juice Nutrition 0.000 description 1
- 229940042129 topical gel Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 230000006871 urological function Effects 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
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- 235000021119 whey protein Nutrition 0.000 description 1
- 235000014101 wine Nutrition 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
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- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
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- 229960002675 xylitol Drugs 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/02—Algae
- A61K36/05—Chlorophycota or chlorophyta (green algae), e.g. Chlorella
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/13—Coniferophyta (gymnosperms)
- A61K36/14—Cupressaceae (Cypress family), e.g. juniper or cypress
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/45—Ericaceae or Vacciniaceae (Heath or Blueberry family), e.g. blueberry, cranberry or bilberry
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8962—Allium, e.g. garden onion, leek, garlic or chives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Description
UROGENITAL AND INTESTINAL DISORDER COMPOSITIONS COMPRISING A SUBSTANCE DERIVED FROM PLANT SPECIES OF THE ERICACEAE FAMILY AND A LACTIC ACID BACTERIA GROWTH FACTOR
TECHNICAL FLELD This application relates to compositions useful in preventing and/or treating urogenital and intestinal disorders
BACKGROUND OF THE INVENTION 0 Complex, microscopic ecosystems pervade the urogenital and intestinal tracts of warm blooded animals Trillions of microorganisms, comprising hundreds of species, occupy the urogenital and intestinal tracts of mammals, influencing and maintaining digestive and urologic functions Microorganisms occupying these regions range from potentially pathogenic strains, such as Escherichia coli, enterococci, Candida, gardnerella, 5 lebsiella and clostridia, to the relatively nonpathogenic, such as lactobacillus and bifidobacterium. Deviations from this delicate floral balance have been etiologically linked to a number of urogenital and/or gastrointestinal tract disorders, such imbalances usually resulting in the proliferation and predominance of pathogenic species Establishing and/or preserving such a delicate floral balance is, therefore, essential to maintaining optimal 0 health
One way of establishing or maintaining the body's flora is by promoting the growth of lactic acid bacteria (e.g., lactobacillus or bifidobacterium) The use of growth factors to treat urogenital and intestinal disorders has been proposed, for instance, in Canadian Patent 1,298,556, issued April 4, 1992 and to Bruce et al., PCT Application Serial 5 Number WO 93/09793, published May 27, 1993, to Reid et al Ideally, such growth factors selectively provide lactic acid bacteria with nutrients and an environment essential for continued growth Despite such selectivity, however, alternative nutrient sources remain available for pathogenic bacteria. Furthermore, growth substrates fail to provide direct activity against offending microorganisms. Therefore, notwithstanding such 0 proposals, there still remains a need for improved urogenital and gastrointestinal tract compositions containing lactic acid bacteria growth factors
The present inventors have found that compositions incorporating plants or extracts of the Ericaceae family with Lactobacillus and/or Bifidobacterium provide improved compositions for treating and/or preventing urogenital and gastrointestinal 5 disorders by modifying the interaction of pathogens with cellular tissue Recent studies also suggest the value of such extracts in treating urinary tract infections Researchers
have observed that various species of Vaccinium (e.g. cranberry and blueberry) contain a high molecular weight compound that inhibits the adhesion of common urinary pathogens (e.g., E. coli) to infection sites within the urinary tract. Ofek I et al., Anti-Escherichia coli Adhesin Activity of Cranberry and Blueberry Juices. N Engl J Med 1991;324;1599. Surprisingly, the compositions of the present invention provide improved environments more conducive to the colonization of lactic acid bacteria.
Accordingly, it is an object of the present invention is to promote a healthy environment for the growth of lactic acid bacteria in the urogenital and gastrointestinal tracts. Another object of the present invention is to provide improved compositions comprising a growth factor for lactic acid bacteria.
A further object of the present invention is to provide compositions for dietary supplementation.
A still further object of the present invention is to provide topical compositions for vaginal use.
An even further object of the present invention is to provide compositions and methods effective in preventing and/or treating urogenital and intestinal disorders.
These and other objects will become readily apparent from the disclosure which follows. SUMMARY OF THE INVENTION
The present invention relates to compositions for the treatment or prevention of urogenital and intestinal disorders, comprising: a.) at least one plant species of the Ericaceae family or its extract; and b.) an effective amount of a growth factor for facilitating the growth of lactic acid bacteria selected from the group consisting of glycogen, rhamnose, gangliosides, salicin, oligosaccharides, galactose, lactulose, methyl-α-D- mannoside, p-nitrophenoi-α-D-mannoside, maltose, dextrin, dextran, levan, sialic acid, acetylglucosamine, yeast extracts, peptone, keratin, vegetable, soy, lauric acid, glycerophosphates and mixtures thereof. The phrase "urogenital and intestinal compositions," as used herein, means a product which in the ordinary course of usage may be retained in the oral cavity, swallowed or applied topically to provide urogenital and/or intestinal activity.
The term "urogenital," as used herein, means that system of organs concerned with the production and excretion of urine and reproduction. The term "intestinal," as used herein, means of or relating to the intestines.
All percentages and ratios used herein are by weight unless otherwise specified Also, all measurements referred to herein are made at 25°C unless otherwise specified DETAILED DESCRIPTION OF THE INVENTION The essential as well as optional components of the compositions of the present invention are described in the following paragraphs.
ESSENTIAL COMPONENTS Plant or Extract of the Family Ericaceae
The Ericaceae (heath) family, consisting of about 110 genera and 4,000 species, is by far the most important family of the Ericales order, encompassing a wide variety of fruit producing shrubbery and evergreen plants Genera falling under Ericaceae family include Vaccinium, Arctostaphylos, Gaultheria, and Gaylussacia The Arctostaphylos genus includes such species as the checkerberry and bearberry (Uva ursi). Other edible fruits such as the creeping snowberry or moxie plum fall under the genus Gaultheria Huckleberries are a well known species of the genus Gaylussacia. The Vaccinium genus, best known for its fruits, contain some of the most common of berries, including the blueberry (e.g., V. australe), cranberry (e.g., V. macrocarpori) and bilberry (e.g , V. myrtillus). The term "berry (ies)," as used herein, means berries, drupes, plums and the like.
E. coli adherence results primarily from adhesins on the raised hair like fimbriae (or pili) of the microorganism. These adhesins are designated MS (mannose-sensitive) and MR (mannose-resistant). Like most fruit, Ericacease fruit species contain fructose, an inhibitor of MS adhesins. However, it has been recently suggested that the plants or extracts of Ericaceae species further contain an unidentified, non-dialyzable polymeric compound which inhibits the MR adhesins associated with pyelonephritogenic strains of E. Coli. The unidentified polymeric compound, as studied in Vaccinium species, was found to inhibit both urinary and fecal isolates of E. Coli, the urinary isolates being inhibited to a greater extent. Ofek, I. et al., Anti-Escherichia coli Adhesin Activity of Cranberry and Blueberry Juices. N Engl J Med 1991 ;324;1599. It has also been reported that the ingestion of large quantities of cranberry juice increased the hippuric acid content of urine by several grams a day. This increase in hippuric acid excretion was accompanied by small decreases in urine pH. In vivo tests have established that hippuric acid was bacteriostatic at pH 5.0 for common pathogens of the urinary tract, but this action was considerably decreased as the urine pH was raised. Papas, N.P., et al., Cranberry Juice In the Treatment of Urinary Tract Infections. Southwestern Medicine, 47:No. 1 (Jan. 1966). That the Ericaceae species of the present invention are effective against other pathogenic
bacteria (e.g., Pseudomonas aeruginosa) is disclosed in U.S. Patent 5,474,774, herein incorporated by reference in its entirety; no effect was observed with respect to adhesion of lactobacillus strains to cells. Without being limited by theory, it is believed that the pathogenic inhibition caused by the Ericaceae plants or extracts results in decreased pathogenic interaction, providing a more favorable, less antagonistic environment for lactobacillus to initially adhere and maintain adherence. The phrase "anti-adhesive activity," as used herein, means an amount effective to inhibit the adhesion of pathogenic microorganisms to the epithelial and/or mucosal lining of the urogenital and/or intestinal tract. Plants or extracts useful in the compositions of the present invention come from a wide range of genera within the Ericaceae family including, but not limited to, Vaccinium, Arctostaphylos, Gaultheria, and Gaylussacia. Preferred species include, V. australe, V. corymbosum, V. occidentale, V. ovatum, V. myrtillus, V. parvifolium, V. uliginosum, V. macrocarpσn, V. oxycoccus, V. erythrocarpum, V. vitis-idaea. V. australe, V. macrocarpon. Vaccinium species most preferred for use in the present invention include V. australe, V. macrocarpon, and V. myrtillus. Mixtures of Ericaceae plants and/or extracts may also be used.
The plants or extracts of the present invention are preferably concentrated, having a ratio of at least about 4 pounds of plant concentrate or extracts per pound of concentrate, more preferably from about 4 pounds of plant concentrates or extracts per pound of concentrate to about 50 pounds of plant concentrate or extracts per pound of concentrate. The Ericaceae extracts are preferably present at a level of at least lOmg, more preferably from about lOOmg to about 18g, most preferably from about 250mg to about 4g per unit dose. The amount of extract contained in each dose of product can be adjusted for the dosage form. For example, the amount of extract in powdered form used in a drink mix can range up to 18g per dose while the amount used in swallowable capsules might range to about 4g. Preferred levels of the Ericaceae plants or extracts provide urinary and/or intestinal tract fluid concentrations of the above mentioned unidentified, non-dialyzable polymeric compound of from about 12 to about 25 micrograms per milliliter. Also, the plants or extracts of the present invention preferably retain greater than 2.5% of their total acid content and greater than about 0.1% of their benzoic acid content. The level selected to provide the desired level of anti-adhesin activity and can be modified as desired. Cranberries and cranberry extracts are useful in the treatment and/or prophylaxis of urinary tract infections and are also useful as vaginal deodorants.
Growth Factor for Lactic acid Bacteria
The compositions of the present invention also incorporate a growth factor for lactic acid bacteria The phrase "a growth factor for facilitating the growth of lactic acid bacteria," as used herein, means a nutrient source or media which supplies a necessary source of food and/or energy for facilitating the growth of lactic acid producing bacteria The growth factor is preferably selective for establishing and maintaining the growth of lactic acid bacteria, preferably Lactobacillus and/or Bifidobacterium species, without facilitating extreme growth of pathogenic bacteria The various nutritional requirements essential for bacterial and/or colony growth are normally met when the growth factor contains fermentable carbohydrate, peptone, meat or yeast extract Supplementations with tomato juice, manganese, acetate and oleic acid esters, especially Tween 80, are stimulatory or even essential for most species and are, therefore, included in most MRS medium Lactic acid bacteria adapted to very particular substrates may require special growth factors. Growth factors suitable for use in the present invention are selected from the group consisting of glycogen; D-mannose; mannitol; escuiine; lactose; saccharose; trehalose; D- raffinose; gentibiose; giuconate; rha nose; gangliosides; salicin, oligosaccharides; galactose, lactulose; methyl-α-D-mannoside; p-nitrophenol-α-D-mannoside, maltose, dextrin, maltodextrin; dextran; levan, sialic acid; acetylglucosamine; yeast extracts, proteinacious materials such as, peptone, keratin, vegetable, soy and unsaturated fatty acids such as lauric acid and teichoic acids such as lipoteichoic acid and esters such as glycerophosphates or β-glycerophosphates. Fiber or fermentable substrates such as psyllium may be used in the present compositions as may gums such as guar gum and xanthan gum. When used vaginally monosaccharides such as fructose and glucose as well as whey proteins may also be incoφorated. The growth factor is preferably selected from the group consisting of rhamnose, oligosaccharides and glucogen
More preferably the growth factor of the present invention is an oligosaccharide such as, but not limited to, galactooligosaccharides, soybean oligosaccharides and fructooligosaccharides. In addition to being a carbohydrate source, oligosaccharides also possess bioadhesive properties which help fix the location of these growth factors for easier access by lactic acid bacteria. Most preferred for use herein are fructooligosaccharides. Lactic acid bacteria, such as Lactobacillus and Bifidobacterium, partially utilize fructooligosaccharides as an energy source by converting it, via fermentation, to lactic acid or a mixture of lactic acid, acetic acid, and CO2 The lactic acid and other fatty acids produced by this carbohydrate fermentation contribute to the
maintenance of low pH which is an important control mechanism for preventing colonization of pathogens.
Chemically, oligofructose is the oligosaccharide fraction of inulin. It is composed of the GFn and Fn type [G = glucose; F = fructose; n - number of frets moieties linked by β (2, 1) linkages in a ratio of about 2: 1, with n = 2-6, and an average degree of polymerization of 4. Inulin is prepared by hot water extraction of chicory roots and is composed of molecules of the GFn type, n ranging as high as 60 with an average degree of polymerization of 10. Fructooligosaccharides suitable for use herein may or may not have non-fructosyl units in place of fructosyl end units. The same is true for other oligosaccharides with respect to their osyl end units. Non-fructosyl units may include, but are not limited to, polyalcohols such as xylitol, mannitol, and sorbitol. Fructooligosaccharides most preferred for use in the present compositions are inulin or oligofructose. Mixtures of these nutrients may also be used.
Without being limited by theory, it is believed that, upon ingestion, growth factors increase the number of Lactobacillus and/or Bifidobacterium species available to displace pathogenic microorganisms from epithelial surfaces. The increase in the number of Lactobacillus and/or Bifidobacterium species competitively exclude the pathogens causing them to be displaced and excreted; the result is an overall reduction of host pathogens. Moreover, as vaginal infections are generally believed to result from pathogenic migrating from the rectum to the vagina, the number of pathogens invading the vagina are also reduced as the number of migratory pathogens decreases.
Growth factors are preferably incoφorated into the compositions of the present invention at from about 5% to about 75%, more preferably from about 20% to about 70%, and most preferably from about 30% to about 65% per unit dose. OPTIONAL COMPONENTS
Species of Lactobacillus or Bifidobacterium
An optional component of the present invention is a viable colony of Lactobacillus or Bifidobacterium. Bacteria of the Lactobacillus genus are characterized as rod-shaped, gram-positive and non-spore-forming bacteria. Of the family Lactobacillaceae, Lactobacillus inhabit the urogenital and gastrointestinal tracts of animals and humans and are important members of lactic acid producing group of bacteria. Various species of Lactobacillus are used commercially in the production of sour milks, cheeses and yogurt. Lactobacilli also share an important role in the manufacture of fermented vegetables (e.g., pickles and sauerkraut), beverages (e.g., beer, wine and juices), sourdough breads, and some sausages.
Lactobacillus species suitable for use in the present invention are those which 1.) readily adhere to the epithelial cells of either the urogenital or gastrointestinal tracts of mammals; 2.) produce hydrogen peroxide; 3.) promote low pH; and produce bacteriocins. By "bacteriocins," as used herein, means proteinaceious, bacteriocidal substances synthesized by bacteria, which usually have a narrow spectrum of activity, inhibiting strains of the same or closely related species. Bacteriocins appear to be capable of displacing or suppressing the growth of other bacteria, and as such may provide an advantage to microorganisms in fermenting the female genital tract ecosystem. Preferred species of Lactobacillus include L. acidophilus, L. johnsonii, L. catenaforme, L. brevis, L. bulgaricus, L. lactis, L. reuterii, L. gasseri, L. helveticυs, L. casei, L. plantarum, L. delbrueckii, L. thermophilis, L. jensenii, L crispatus, L. rogosae and L. fermentum. Species of Lactobacillus most preferred for use in the compositions of the present invention include L. acidophilus, L. casei, L. crispatus, L. fermentum, and L. plantarum. Preferably, the Lactobacillus species of the present invention are hydrogen peroxide producing such as L. acidophilus, L. catenaforme, L. casei, L. crispatus, L. delbrueckii, L. jensenii, L rogosae. L. fermentum, L. gasseri and L. plantarum are also preferred for use herein in view of their adhesive properties.
Also inhabiting the urogenital and gastrointestinal tracts of mammals and useful to the compositions of the present invention are species of the genus Bifidobacterium (family Actinomycetaceae). Bifidobacterium species are non-acid-fast, nonmotile gram negative rods. Lactic and acetic acid producing Bifidobacteria are also considered important regulators of the urogenital and intestinal flora of mammals. Species suitable for use in the present compositions include, but are not limited to, B. longum, B. breve, Lactobacillus Bifidus and Lactobacillus bifidus subsp pennsylvanicus. Preferred for use in the present compositions is B. Bifidum, most preferred B. Bifidum subsp. Pennsylvanicus.
Mixtures of the Lactobacillus and/or Bifidobacterium species may also be used. Any of the above species may be obtained either commercially or through laboratory cultures.
The Lactobacillus and/or Bifidobacterium species are present at levels of at least about 10^ cells per unit dose, preferably at levels of from about 10^ to about 10^2 cens per unit dose and most preferably at levels of from about 10^ to about 10^ cells per unit dose. The phrase "unit dose," as used herein, means physically discrete units suitable as unitary dosages for administration to mammals, each such unit containing a predetermined quantity of an active ingredient calculated to produce the desired therapeutic effect in association with pharmaceutically acceptable carriers. The level is selected to provide the
desired level of urogenital and gastrointestinal activity and can be modified as desired. Lactobacillus may loose 4-6 fold of its viability at room temperature and during manufacturing, so depending on the manufacturing conditions, an excess of Lactobacillus is added to maintain an adequate number of viable organisms per final unit dose form. Alternatively, a patient can be administered the equivalent of these concentrations of organisms where the values are expressed by some other measurement such as, for example, total protein concentration. Buffering Agents
The compositions of the present invention may also contain a buffering agent. For oral compositions, buffering to an acidic pH to enhance flavor may be done. For products used in the vaginal area, buffering agents suitable for use in the compositions of the present invention are those capable of maintaining a urogenital pH of 3.0 to 5.5. Any mild pharmaceutically acceptable acid, other than those found in the Ericaceae species disclosed herein, can be used. Suitable acids include boric acid, or organic acids such as quinnic acid, proprionic acid, malic acid, pyruvic acid, hippuric acid, tartaric acid, sorbic acid, benzoic acid, lactic acid, ascorbic acid, citric acid, or acetic acid, in combination with their respective sodium or other pharmaceutically acceptable salt (to the extent necessary to achieve the desired pH). When buffered, the compositions of the present invention are preferably buffered to a pH range of from about 3.5 to about 5.0, preferably from about 3.7 to about 4.7, and preferably using lactic acid with sodium lactate or a combination lactic acid/sodium lactate and benzoic acid or lactic acid/sodium lactate and proprionic acid. Additional Plant Extracts
Additional therapeutic and/or medicinal plants or extracts may also be incoφorated into the compositions of the present invention. Such plants or extracts include echinacea, allium, bucha, juniper ginseng, allicin, chloretla, aigin and the like. Mixtures of these additional plants or extracts may also be used. Nutritional Additives
Nutritional additives may also be incoφorated into the compositions of the present invention. Such additives include, but are not limited to, proteins and carbohydrates other than those mentioned herein as growth factors, vitamins such as nicotinic acid, pantothenic acid, and riboflavin; minerals such as manganese; phytochemicals; amino acids such as serine, glutamine, methionine, glycine, cysteine, leucine, isoleucine, threonine, valine.
Pharmaceutical Actives
The compositions of the present invention may also be used in combination with pharmaceutical actives. The pharmaceutical active is preferably selected from at least one of an analgesic agent and/or a gastrointestinal agent. Examples of analgesics preferred for use in the present invention include acetaminophen, acetyl salicylic acid, indomethacin and optically active isomers or racemates of ibuprofen, naproxen, flurbiprofen, caφrofen, tiaprofenic acid, cicloprofen, ketoprofen, ketorolac, etodolac, indomethacin, sulindac, fenoprofen, diclofenac, piroxicam, benzydomine, nabumetone, their pharmaceutically acceptable salts and mixtures thereof.
Examples of gastrointestinal agents preferred for use in the present invention include anticholinergics including atropine, clidinium and dicyclomine; antacids including aluminum hydroxide, bismuth subsalicylate, bismuth subcitrate, simethicone, calcium carbonate and magaldrate; H2~receptor antagonists including cimetidine, famotidine, nizatidine and ranitidine; laxatives including: docusate, phenolphthalein and casanthrol; gastroprotectants including sucralfate and sucralfate humid gel; gastrokinetic agents including metoclopramide and cisapride; proton pump inhibitors including omeprazole and antidiarrheals including: diphenoxylate, kaolin pectin, attapulgite and loperamide. Carrier Materials The carriers into which the compositions of the present invention may be incorporated are many and varied and depend largely upon the end use of the compositions. These carriers include orally acceptable as well as topical compositions. They may be completely inert or contain or may be other active ingredients, yet the carriers must be compatible with the herein disclosed compositions. The term "compatible," as used herein, means that the carrier components are capable of being commingled with the components of the present invention, and with each other, in a manner such that there is no interaction which would substantially reduce the activity of the compositions under ordinary use situations. Carrier materials must, of course, be of sufficiently high purity and sufficiently low toxicity to render them suitable for administration to the human being treated. Preferably the compositions of the present invention comprise from about 0.01% to about 99.99% of one or more carrier materials.
Carriers suitable for topical administration of the present compositions include suppositories, vaginal tablets or capsules, ovules, creams, solutions for lavages, emulsions, foams, soaps, gels, liniments, oils and ointments.
Creams and gels, other base formulations may be used in topical administration of the present compositions to, for example, the genital region and are prepared according to conventional methods for semi-solid compositions using excipients like vaseline, paraffin, vaseline oil, vegetable oils, animal oils, solid and liquid synthetic glycerides, waxes, lanolin, lanolin alcohols, sorbitan esters, fatty alcohols, liquid/solid polyethylene glycols, propylene glycols, polyethylene, starch, acrylamides, methacrylamides, derivatives of cellulose and carboxyvinylpolymers.
Ovules, suppositories, vaginal capsules or tablets and effervescent tablets may also be useful in topical application of the prevention. Ovules are similar to suppositories, ovoidal shaped and the excipients mainly used are semi-synthetic glycerides and polyethylene glycols and optionally also emulsifiers and surfactants.
The vaginal capsules are gelatinous envelopes or sachets within which is subdivided the suspension which is generally anhydrous and contains liquid paraffin, vaseline, vegetable oils and semi-synthetic oils and thickening agents. The tablets, shaped suitably for vaginal use, contain as main excipients lactose, starch, polyvinylpyrrolidone, cellulose derivatives, magnesium stearate, glycol. The effervescent tablets contain chemical components (i.e. sodium bicarbonate with citric acid or tartaric acid), which are necessary to develop carbon dioxide in order to produce effervescence.
The compositions of the present invention may also be incoφorated into and topically applied by woven or nonwoven fabric materials such as tissues, wipes, feminine napkins, panty liners, tampons, diapers, incontinent care products and the like. Preferred for use herein are nonwoven fabrics. Nonwoven fabrics suitable for incoφorating the present compositions are described in U.S. Patent 4,891,227 to Tha an et al., herein incoφorated by reference. Oral dosage forms are also useful as carriers for the present invention. These dosage forms contain compatible solid or liquid filler diluents or encapsulating substances which are suitable for oral administration to a human or lower animal.
Liquid dosage forms for oral administration may comprise dissolving or suspending the compositions of the present invention in a potable liquid, such as sterile or distilled water. Alternatively, liquid or dry oral administration forms can comprise an enterically coated capsule containing the dosage forms. Suitable forms include emulsions, suspensions, solutions, syrups, and elixirs containing inert diluents commonly used in the art, such as purified water, sugars, polysaccharides, silicate gels, gelatin, or an alcohol. These inert diluents do not actively participate in the therapeutic effect of the present invention. Besides the inert diluents, such compositions can also contain wetting agents,
emulsifying agents, suspending agents, as well as additional therapeutic actives For a more detailed description of liquid and liquid-like dosage forms, see Remington's Pharmaceutical Sciences. 17th ed., Mack Publishing Company, Easton, Pa. (1990), pages 1519-1544, herein incoφorated by reference. Tablets can be compressed, molded, triturated or multiple compressed, containing suitable binders, lubricants, diluents, disintegrating agents, and flow-inducing agents.
Tablets may be enteric-, film- or sugar-coated Protein-like coating components may also be included. Useful for improvement of gastrointestinal disorders, such components may contain branched amino acid-modified proteins. Whey powders, for example, are treated with papain in the presence of the amino acids ethyl L-leucine (16.1 parts), ethyl L- isoleucine (7.4 parts), ethyl L-valine (10.2 parts), cysteine hydrochloride (1.5 parts), and sodium carbonate (26 parts) in water at 40°C for 20 minutes to manufacture coated powders containing 10% free amino acids and 43% branched amino acids. The branched amino acid-modified powders can be mixed with fats, dextrins, salts, vitamins, and the like to make tablets.
Other examples of a tablet coating materials are zeolites and clays to make tablets more palatable. Zeolites have found use as bacterial feed coatings for domestic animals. For example, in the domestic animal business, timeline fumarate is dissolved in methanol, supported on mordenite-type zeolite or starch, dried and further premixed with the supports to produce sustained-release, coated granules. Still other examples of tablet coatings include complex carbohydrate and inclusion complexes.
Also useful are soft or hard gelatin capsules. Preferably, the gelatin shell is essentially transparent so as to enhance the aesthetic qualities of the capsule. Soft and hard gelatin shells generally comprise gelatin, a plasticizer and water. The starting gelatin material generally used in the manufacture of these capsules is obtained by the partial hydrolysis of collagenous material. Gelatin suitable for capsule manufacture is commercially available from the Sigma Chemical Company, St. Louis, Mo. One or more plasticizers is incoφorated to produce a gelatin shell. Useful plasticizers of the present invention include glycerin, sorbitan, sorbitol, or similar low molecular weight polyols, and mixtures thereof.
Techniques and compositions for making solid oral dosage forms are described in Marshall, "Solid Oral Dosage Forms," Modern Pharmaceutics. Vol. 7. (Banker and Rhodes, editors), 359-427 (1979), incoφorated by reference herein. Techniques and compositions for making tablets (compressed and molded), capsules (hard and soft gelatin), troches and pills are described in Remington's Pharmaceutical Sciences (Arthur
Osol, editor), 1553-1593 (1980) and U.S. Patent 4,935,243, to Borkan et al., issued June 19, 1990; these two references being incoφorated herein by reference in their entirety. Specific examples of pharmaceutically acceptable carriers and excipients that may be used to formulate oral dosage forms, are described in U.S. Patent 3,903,297, Robert, issued September 2, 1975, incoφorated by reference herein.
Alternatively, the compositions of the present invention may be achieved by incoφorating the compositions of the present invention into freeze-dried or lyophilized tablets. Freeze-drying or lyophilization facilitates disintegration of the composition by forming the dried composition into an open matrix network. In most cases, this results in rapid permeation by the aqueous media, promoting timely delivery of the product. Suitable methods of freeze drying are well known in the art and commonly employed. Any suitable conventional method of freeze-drying may be utilized. A preferable method of freezing and drying is to fast freeze the composition and then dry the composition to a final moisture content of about 2% to about 5%. Suitable methods of freeze-drying and production are taught by U.S. Patent 4.642.903. February 17, 1987, to Davies, U.S. Patent 4.946.684. August 7, 1990, to Blank et al., U.S. Patents 4.305.502 and 4.371.516 . issued December 15, 1981 and February 1, 1983 respectively, to Gregory et al., and U.S. Patent 5.188.825. February 23,1993, to lies et al.; which are all incoφorated herein by reference. Similarly, the compositions of the present invention may be vacuum dried.
Vacuum drying involves at least the partial drying of compositions at temperatures above compositions' collapse temperature. Freeze drying, on the other hand, involves the drying of compositions at temperatures below the composition's collapse temperature. Any suitable method of vacuum drying may be used. Suitable vacuum drying processes are described in U.S. Patent 5.298.261. to Pebley et al., issued March 29, 1994, herein incoφorated by reference.
One other form of tableting technology that may be applicable to the present invention is a liquid/liquid extract developed by Janssen Pharmaceutica Inc. and is identified by the trade name Quicksolv™. This technology is fully described in U.S. Patent 5.215.756. herein incoφorated by reference.
Other optional ingredients well known to the pharmacist's art may also be included in amounts generally known for these ingredients, for example, natural or artificial sweeteners, flavoring agents, colorants, perfuming agents, buffering agents and the like to provide a palatable and pleasant looking final product, antioxidants, for example, butylated hydroxy anisole or butylated hydroxy toluene, and preservatives, for example, methyl or
propyl paraben, potassium sorbate, or sodium benzoate, to prolong and enhance shelf life. A preferred optional component is also caffeine.
Those of ordinary skill in the art will quickly realize other suitable ingredients, diluents and dosage forms, or will be able to ascertain such, using routine experimentation. Further, the administration of the various compositions can be carried out using standard techniques common to those of ordinary skill in the art.
Examples The following examples further describe and demonstrate embodiments within the scope of the present invention. These examples are strictly given for illustration puφoses and are not to be construed as limitations of the present invention, as many variations are possible without departing from the spirit and scope of the invention as set forth herein.
Example I A tablet form of the present invention is made by combining the following components using conventional mixing and tableting technology. Ingredient % Weight
Concentrated Cranberry Extract 17.600% fructooligosaccharide 1 56.340%
Ethylcellulose, 100 cps (5% ethanol soln) 9.900% Starch 11.230% Talc 4.230%
Stearic Acid 0.700%
1 Available as NutraFlora FOS from Golden Technologies Company, Inc.
The cranberry extract and fructooligosaccharide are granulated with 5% ethylcellulose in ethanol. The granulation is then passed through a 12 mesh screen and dried at 120°F. To the dried granulation is added stearic acid. The granulation mixture is passed through a 20 mesh screen. To the sieved granulation is added the starch and talc and mixing until uniform. The resultant granulation mixture is then compressed using conventional tableting processes.
Example II A capsule form of the present invention is made by combining the following components using conventional mixing technology.
Ingredient % Weight
Concentrated Cranberry Extract 35.000% fructooligosaccharide * 35.000% Avicel2 26.300%
14
Ac Di Sol3 3.700%
1 Available as NutraFlora FOS from Golden Technologies Company, Inc.
2 TM for microcrystalline cellulose, a highly purified particulate form of cellulose.
3 A brand of a cross-linked form of sodium carboxymethylcellulose. Combine and mix the cranberry extract, fructooligosaccharide, Avicel and Ac Di
Sol in a V-blender until uniform. Unit dose amounts of the resultant mixture is then placed into suitably sized hard gelatin capsules.
Example III A topical gel form of the present invention is made by combining the following components using conventional mixing technology.
Ingredient % Weight
Concentrated Cranberry Extract 0.50% fructooligosaccharide 1 6.00%
Polyacrylamide and C13_ι4 Isoparaffin and Laureth-72 4.00%
PPG- 14 Butylether 8.00%
Water, Purified q.s.
* Available as NutraFlora FOS from Golden Technologies Company, Inc. 2 Available as Sepigel from Seppic Coφoration. Water is added to a suitable size container. While mixing at a moderate speed (300 φm), the Polyacrylamide and C 13.1 Isoparaffin and Laureth-7 is added to the water to form a water phase. Separately, the PPG- 14 Butyl ether is placed in a container and covered. Using a Lightnin' Mixer with a 3 blade paddle prop, the cranberry extract and fructooligosaccharide are added to the PPG- 14 Butyl ether and mixed at a low speed (100 φm) until the cranberry extract and fructooligosaccharide are dissolved. The PPG- 14 Butyl ether mixture is slowly added to the water phase to form a gel. The resulting gel is mixed at moderate speed until uniform.
Furthermore, the above described compositions may also contain a growth factor such as glycogen, rhamnose, oligosaccharides, lactulose, methyl-α-D-mannoside, p- nitrophenol-α-D-mannoside, maltose, dextrin, levan, acetylglucosamine, amino acids, proteinacious materials such as, peptone, keratin, vegetable, soy, glycerophosphates and mixtures thereof. Those skilled in the art will quickly realize other suitable ingredients, diluents and dosage forms (or readily ascertain such using routine experimentation) which may further be incoφorated into the above compositions without departing from the scope and spirit of the present invention.
While the invention has been described in terms of its preferred embodiments, those skilled in the art will recognize that the invention can also be practiced by administering the herein described components separately and still remain within the scope and spirit of the present invention.
Claims (10)
1. A composition for treating urogenital and intestinal disorders, comprising: a.) at least one plant species of the Ericaceae family or its extract; and b.) an effective amount of a growth factor for facilitating the growth of lactic acid bacteria selected from the group consisting of glycogen, rhamnose, gangliosides, salicin, oligosaccharides, galactose, lactulose, methyl-α-D- mannoside, p-nitrophenol-α-D-mannoside, maltose, dextrin, dextran, levan, sialic acid, acetylglucosamine, yeast extracts, peptone, keratin, vegetable, soy, lauric acid, glycerophosphates and mixtures thereof.
2. A composition according to Claim 1, further comprising a viable culture of at least one species of bacteria selected from the group consisting of lactobacillus, bifidobacterium and mixtures thereof.
3. A composition according to Claims 1 or 2 wherein growth factor is an oligosaccharide selected from the group consisting of galactooligosaccharides, soybean oligosaccharides, fructooligosaccharides and mixtures thereof.
4. A composition according to any one of the preceding Claims, wherein the plant or extract is from species selected from the genus selected from the group consisting of Vaccinium, Arctostaphylos and mixtures thereof.
5. A composition according to any one of the preceding Claims, further comprising an additional plant extract selected from the group consisting of echinacea, allium, bucha, juniper ginseng, allicin, chlorella, algin and mixtures thereof and/or a nutritional additive selected from the group consisting of proteins, carbohydrates, vitamins, minerals, amino acids, phytochemicals and mixtures thereof and/or a pharmaceutical active selected from the group of consisting of analgesics, gastrointestinal actives and mixtures thereof.
6. A composition according to any one of the preceding Claims, further comprising a carrier selected from group consisting of tablet, troche, oral liquid, suspension, capsule, gelatin capsule.
7. A topically administered composition for treating urogenital disorders, comprising: a.) at least one plant species of the Ericaceae family or its extract; and b.) an effective amount of a growth factor for facilitating the growth of lactic acid bacteria selected from the group consisting of glycogen, rhamnose, oligosaccharides, lactulose, methyl-α-D-mannoside, p-nitrophenol-α-D- mannoside, maltose, dextrin, levan, acetylglu-cosamine, proteinacious materials such as, peptone, keratin, vegetable, soy, glycerophosphates and mixtures thereof.
8. A composition according to Claim 7, wherein the growth factor is an oligosaccharide selected from the group consisting of galactooligosaccharides, soybean oligosaccharides, fructooligosaccharides and mixtures thereof.
9. A composition according to Claim 7 or 8, further comprising a buffering agent and wherein the composition is buffered to a pH of from about 3.5 to about 5.
10. A composition according to any of Claims 7, 8, or 9, further comprising a carrier selected from group consisting of suppository, vaginal tablet, vaginal troche, vaginal gelatin capsule, cream, gel, ointment, lotion, irrigant, douche, tissue, wipe, panty liner, feminine napkin, tampon, diaper and incontinent care product.
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US60148296A | 1996-02-14 | 1996-02-14 | |
US601482 | 1996-02-14 | ||
US63009696A | 1996-04-09 | 1996-04-09 | |
US630096 | 1996-04-09 | ||
PCT/US1997/001665 WO1997029763A1 (en) | 1996-02-14 | 1997-02-06 | Urogenital and intestinal disorder compositions comprising a substance derived from plant species of the ericaceae family and a lactic acid bacteria growth factor |
Publications (1)
Publication Number | Publication Date |
---|---|
AU1854297A true AU1854297A (en) | 1997-09-02 |
Family
ID=27083871
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU18542/97A Abandoned AU1854297A (en) | 1996-02-14 | 1997-02-06 | Urogenital and intestinal disorder compositions comprising substance derived from plant species of the ericaceae family and a lactic acid bacteria growth factor |
Country Status (6)
Country | Link |
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EP (1) | EP0881905A1 (en) |
JP (1) | JPH11504049A (en) |
CN (1) | CN1211189A (en) |
AU (1) | AU1854297A (en) |
CA (1) | CA2246371A1 (en) |
WO (1) | WO1997029763A1 (en) |
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CN1120000C (en) * | 1997-11-24 | 2003-09-03 | 曾忠铭 | Pharmaceutical formulation for stimulating the growth of gram-positive bacilli and increasing the acidity in vagina and use thereof |
US6192887B1 (en) * | 1998-05-19 | 2001-02-27 | The Pennsylvania State University | Broad spectrum microbicidal and spermicidal compositions and methods having activity against sexually transmitted agents including papillomaviruses |
US6080401A (en) * | 1998-11-19 | 2000-06-27 | Reddy; Malireddy S. | Herbal and pharmaceutical drugs enhanced with probiotics |
NZ517941A (en) | 1999-09-06 | 2003-08-29 | Effem Foods | Food product and process for manufacturing same |
DE19948419A1 (en) * | 1999-10-07 | 2001-04-12 | Symbio Herborn Group Gmbh & Co | Tampon for use in body cavities |
SE9904289D0 (en) | 1999-11-26 | 1999-11-26 | Niklas Arnberg | Method and camposition for the treatment of adenoviral ocular infections |
FI109602B (en) | 2001-01-25 | 2002-09-13 | Valio Oy | Probiotkombination |
EP1243273A1 (en) * | 2001-03-22 | 2002-09-25 | Societe Des Produits Nestle S.A. | Composition comprising a prebiotic for decreasing infammatory process and abnormal activation of non-specific immune parameters |
US6521270B1 (en) * | 2001-06-11 | 2003-02-18 | The Procter & Gamble Company | Compositions comprising nitrofurantoin and uva ursi |
EP1319410A1 (en) * | 2001-12-11 | 2003-06-18 | Société des Produits Nestlé S.A. | Use of micro-organisms for a directed delivery of substances to specific parts of the gut |
KR20030066902A (en) * | 2002-02-06 | 2003-08-14 | 주식회사 코리즈 | Composition including levan as growth stimulator for intestinal lactic acid-producing bacteria |
GB0229015D0 (en) | 2002-12-12 | 2003-01-15 | Novartis Nutrition Ag | New Compound |
GB0230042D0 (en) * | 2002-12-23 | 2003-01-29 | Britannia Pharmaceuticals Ltd | Composition comprising plant extract and a sugar for use in inhibiting bacterial proliferation |
ATE513551T1 (en) * | 2003-01-24 | 2011-07-15 | Flora Technology Inc | COMPOSITIONS AND METHODS FOR RESTORING BACTERIAL FLORA |
FR2856304B1 (en) * | 2003-06-20 | 2006-03-03 | Natural Product Consulting | COMPOSITION FOR THE PREVENTION OF INFECTIONS OF THE URINARY SYSTEM |
US20050019379A1 (en) * | 2003-07-22 | 2005-01-27 | Kimberly-Clark Worldwide, Inc. | Wipe and methods for improving skin health |
US7785640B2 (en) | 2004-01-16 | 2010-08-31 | Amerilab Technologies, Inc. | Effervescent composition including cranberry extract |
US8110215B2 (en) | 2004-04-30 | 2012-02-07 | Kimberly-Clark Worldwide, Inc. | Personal care products and methods for inhibiting the adherence of flora to skin |
EP1600060A1 (en) * | 2004-05-25 | 2005-11-30 | Cognis IP Management GmbH | Oral and/or topical compositions comprising prebiotics and fatty acid |
EP1600062A1 (en) * | 2004-05-25 | 2005-11-30 | Cognis IP Management GmbH | Oral and/or topical compositions comprising prebiotics and sterols |
EP1614357A1 (en) * | 2004-07-10 | 2006-01-11 | Cognis IP Management GmbH | Dietary supplements comprising prebiotics and fatty acid |
FR2874825B1 (en) * | 2004-09-08 | 2006-12-08 | Genibio Sarl | USES OF BENEFICIAL PREBIOTIC OLIGOSACCHARIDES FOR VAGINAL FLORA |
WO2006114061A1 (en) | 2005-04-27 | 2006-11-02 | Shenzhen Phlora Biotechnology Limited | A composition and method of regulating and maintaining the vaginal bacterial flora and the normal acidity in the vaginal |
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JPWO2008081834A1 (en) * | 2006-12-28 | 2010-04-30 | 江崎グリコ株式会社 | Foods containing glycogen and their uses |
WO2009047537A1 (en) * | 2007-10-11 | 2009-04-16 | Fayrefield Foods Limited | Preparation for treating intestinal infection comprising oligosaccharides and insoluble cellular material |
US20110064706A1 (en) * | 2008-01-11 | 2011-03-17 | U.S. Nutraceuticals, Llc D/B/A Valensa International | Method of preventing, controlling and ameliorating urinary tract infections and supporting digestive health by using a synergistic cranberry derivative, a d-mannose composition and a proprietary probiotic blend |
KR101257914B1 (en) * | 2008-06-24 | 2013-05-06 | 모리나가 뉴교 가부시키가이샤 | Diluting solution for suspension for use in the measurement of number of living microbial cells contained in sample, and method for measurement of number of living microbial cells |
US20100210600A1 (en) * | 2009-02-19 | 2010-08-19 | Prelief Inc. | Methods and Compositions for Treating Urogenital Disorders |
ITMI20110792A1 (en) | 2011-05-09 | 2012-11-10 | Probiotical Spa | STRAINS OF BACTERIA BELONGING TO THE BIFIDOBACTERIUM TYPE FOR USE IN THE TREATMENT OF HYPERCOLESTEROLEMIA. |
ITMI20110791A1 (en) | 2011-05-09 | 2012-11-10 | Probiotical Spa | BACTERIA OF BACTERIA ABLE TO METABOLIZE THE OXALATES. |
ITMI20110793A1 (en) | 2011-05-09 | 2012-11-10 | Probiotical Spa | STRAINS OF PROBIOTIC BACTERIA AND SYNBIOTIC COMPOSITION CONTAINING THEMSELVES INTENDED FOR THE BABY FOOD. |
EP2662086A1 (en) * | 2012-05-08 | 2013-11-13 | Progressare Medinvest B.V. | Composition for the treatment or prevention of urinary tract infections and dosage form |
ITMI20130793A1 (en) * | 2013-05-14 | 2014-11-15 | Probiotical Spa | COMPOSITION INCLUDING LACTIC BACTERIA FOR USE IN THE PREVENTIVE AND / OR CURATIVE TREATMENT OF THE RECURRENT CYCLES. |
US11166968B2 (en) | 2015-09-29 | 2021-11-09 | Kimberly-Clark Worldwide, Inc. | Synergistic composition for maintenance of healthy balance of microflora |
WO2017058174A1 (en) * | 2015-09-29 | 2017-04-06 | Kimberly-Clark Worldwide, Inc. | Composition for maintaining loctobacillus dominance |
RU2637650C2 (en) * | 2016-03-29 | 2017-12-05 | Общество с ограниченной ответственностью "ОКТАВА ХОЛДИНГ" | Composition for prevention of urinary tract diseases |
EP3320897A1 (en) * | 2016-11-14 | 2018-05-16 | Dompè Primary S.r.l | Process for the preparation of coated cranberry granules with stable proanthocyanidine content |
MX2019006193A (en) * | 2016-11-30 | 2019-08-21 | Probioswiss Ag | Urogenital medical device formulation based on suitable biochemical compositions for the stabilization of the acidity and the redox state of the vaginal fluid. |
CN113662175B (en) * | 2021-08-16 | 2022-05-03 | 广州市沐家健康产业有限公司 | Plant-based enzyme liquid composition for expelling toxin and beautifying and preparation method thereof |
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SU1708342A1 (en) * | 1989-10-04 | 1992-01-30 | Научно-производственное объединение "Аэрозоль" | After-shave cream |
JPH0416163A (en) * | 1990-05-02 | 1992-01-21 | Nippon Synthetic Chem Ind Co Ltd:The | Intestine-controlling composition |
FR2678166B1 (en) * | 1991-06-27 | 1993-10-22 | Bioeurope | COSMETIC COMPOSITIONS CONTAINING GLUCOOLIGOSACCHARIDES. |
US5474774A (en) * | 1994-03-25 | 1995-12-12 | Jlb, Inc. | Adhesion inhibiting composition |
JPH0919276A (en) * | 1995-07-06 | 1997-01-21 | Roozu Mei:Kk | Healthy beauty beverage |
-
1997
- 1997-02-06 CA CA002246371A patent/CA2246371A1/en not_active Abandoned
- 1997-02-06 AU AU18542/97A patent/AU1854297A/en not_active Abandoned
- 1997-02-06 CN CN97192256A patent/CN1211189A/en active Pending
- 1997-02-06 JP JP9529374A patent/JPH11504049A/en active Pending
- 1997-02-06 EP EP97904185A patent/EP0881905A1/en not_active Withdrawn
- 1997-02-06 WO PCT/US1997/001665 patent/WO1997029763A1/en not_active Application Discontinuation
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WO1997029763A1 (en) | 1997-08-21 |
CN1211189A (en) | 1999-03-17 |
CA2246371A1 (en) | 1997-08-21 |
EP0881905A1 (en) | 1998-12-09 |
JPH11504049A (en) | 1999-04-06 |
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