EP0880354A1 - Urogenital and intestinal compositions - Google Patents
Urogenital and intestinal compositionsInfo
- Publication number
- EP0880354A1 EP0880354A1 EP97904914A EP97904914A EP0880354A1 EP 0880354 A1 EP0880354 A1 EP 0880354A1 EP 97904914 A EP97904914 A EP 97904914A EP 97904914 A EP97904914 A EP 97904914A EP 0880354 A1 EP0880354 A1 EP 0880354A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- acid
- lactobacillus
- species
- group
- mixtures
- 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.)
- Withdrawn
Links
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- 230000000968 intestinal effect Effects 0.000 title description 7
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- 229940039696 lactobacillus Drugs 0.000 claims abstract description 55
- 241000894006 Bacteria Species 0.000 claims abstract description 31
- 239000000284 extract Substances 0.000 claims abstract description 25
- 241000186000 Bifidobacterium Species 0.000 claims abstract description 24
- 241000894007 species Species 0.000 claims abstract description 24
- 241000208421 Ericaceae Species 0.000 claims abstract description 19
- 241000196324 Embryophyta Species 0.000 claims abstract description 18
- 208000025609 Urogenital disease Diseases 0.000 claims abstract description 9
- 208000028774 intestinal disease Diseases 0.000 claims abstract description 7
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 40
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- 239000004310 lactic acid Substances 0.000 claims description 20
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- 238000000576 coating method Methods 0.000 claims description 18
- 239000000463 material Substances 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 14
- 239000011248 coating agent Substances 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 229920001542 oligosaccharide Polymers 0.000 claims description 11
- 150000002482 oligosaccharides Chemical class 0.000 claims description 11
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- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 claims description 10
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
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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)
- A61K36/88—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
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- 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
Definitions
- compositions useful in preventing and/or treating urogenital and intestinal disorders This application relates to compositions useful in preventing and/or treating urogenital and intestinal disorders.
- Deviations from this delicate flora 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 flora balance is, therefore, essential to maintaining optimal health.
- lactobacillus One way of establishing or maintaining the body's flora is by administering lactobacillus.
- lactobacillus to treat urogenital and intestinal disorders has been proposed, for instance, in Canadian Patent 1,298,556, issued April 4, 1992, to Bruce et al., PCT Application Serial Number WO 93/09793, published May 27, 1993, to Reid et al. and U.S. Patent 5,176,911, issued January 5, 1995, to Tosi et al.
- lactobacillus provide host protection via adherence to intestinal or vaginal epithelial cells.
- Bifidobacterium provide improved compositions for treating and/or preventing urogenital and gastrointestinal disorders by modifying the interaction of pathogens with cellular tissue. Recent studies also suggest the value of Ericaceae extracts in treating urinary tract infections. -Researchers have observed that various species of Vaccinium (e.g. cranberry and blueberry) contain a polymeric compound which inhibits the adhesion of common urinary pathogens (e.g., E. coli) to infection sites within the urinary tract.
- Vaccinium e.g. cranberry and blueberry
- 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 to provide compositions for dietary supplementation.
- Another object of the present invention is to provide improved compositions comprising a viable colony of microencapsulated lactobacillus and/or bifidobacteria.
- a further object of the present invention is to provide compositions effective in preventing and/or treating urogenital and intestinal disorders.
- 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 methods for preventing and/or treating urogenital and intestinal disorders.
- the present invention relates to compositions for the treatment or prevention of urogenital and intestinal disorders, comprising: a.) an antiadhesive amount of at least one plant species of the Ericaceae family or its extract; and b.) a viable culture of at least one species of microencapsulated bacteria selected from the group consisting of lactobacillus, bifidobacterium and mixtures thereof
- the present invention also relates to the above compositions further comprising a growth factor for facilitating the growth of lactic acid bacteria.
- urogenital and intestinal compositions 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.
- antiadhesive amount means an amount effective to reduce the number of pathogenic microorganisms on the epithelial and/or mucosal lining of the urogenital and/or intestinal tract.
- urogenital means that system of organs concerned with the production and excretion of urine and reproduction.
- intestinal means of or relating to the intestines.
- nonpathogenic means substantially lacking the ability to cause disease or abnormality in healthy mammals.
- health means free of underlying disease and/or immunosuppression
- the Ericaceae (heath) family consisting of about 1 10 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 rsi).
- 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).
- blueberry e.g., V. australe
- cranberry e.g., V. macrocarpori
- bilberry e.g., V. myrtillus
- 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-resistent).
- Plants or extracts useful in the compositions of the present invention come from a wide range of Ericaceae genera including, but not limited to, Vaccinium, Arctostaphylos, Gaultheria, and Gaylussacia.
- Preferred species include, V. australe, V. corymbosum, V. occidental, V. ova turn, V. myrtillus, V. parvifolium, V. uliginosum, V. macrocarpon, V. oxycoccus, V. erythrocarpum, V. vitis-idaea.
- Vaccinium species most preferred for use in the present invention include V. australe, V. macrocarpon, and V. myrtillus.
- 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 1 Omg, 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.
- 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.
- 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 is 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. Species of Lactobacillus or Bifidobacterium
- Lactobacillus Another essential component of the present invention is a viable colony of microencapsulated Lactobacillus or Bifidobacterium.
- Bacteria of the Lactobacillus genus are characterized as rod-shaped, gram-positive and non-spore-forming bacteria.
- 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.
- bacteriocins 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. catenqforme, L.
- Lactobacillus species of the present invention are hydrogen peroxide producing such as L. acidophilus, L. catenqforme, L. casei, L.
- Bifidobacterium family Actinomycetaceae
- 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.
- 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.
- 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 as core and/or coating components at levels of at least about 10 ⁇ cells per unit dose, preferably at levels of from about 10"* to about 1012 cells per unit dose and most preferably at levels of from about 10 > to about 10 * ⁇ cells per unit dose
- unit dose 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.
- 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
- the Lactobacillus and/or Bifidobacterium species of the present invention must also be microencapsulated.
- Viable Lactobacillus and/or Bifidobacterium bacteria that have been lyophilized after the removal of the growth media can be used for encapsulation
- the bacteria can be obtained from commercial sources, or can be obtained from laboratory strains.
- Suitable media include MRS, Thayer-Martin media, Trypticase Soy, Brain-Heart Infusion Broth, or any other enriched media suitable for the cultivation of these organisms, as no particular media is critical to the success of this suppository
- the only important factors are the viability and quantity of the micro-organisms that are always determined by standard clinical laboratory dilution methods, such as plating the quantified dilution of bacteria on to blood agar plates or other enriched media, incubating at 37°C for 24-48 hours in a 5-10% carbon dioxide atmosphere, and then performing a colony count
- the removal of the nutrient media is done by centrifugation at 14,000 x g at 0°-4°C, and then washing with sterile, balanced salts and 5% glucose solution at least three times after the initial centrifugation.
- compositions of the present invention is a growth factor for facilitating the growth of lactic acid bacteria.
- a growth factor for facilitating the growth of lactic acid bacteria is meant 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, 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 contain fermentable carbohydrate, peptone, meat and yeast extract.
- growth factors include, but are not limited to, yeast extracts; gangliosides; salicin; mono-, di- and polysaccharide sugars such as glycogen, glucose, fructose, rhamnose, lactulose, methyl- ⁇ -D-mannoside, p-nitrophenol- ⁇ -D-mannoside, maltose, maltodextrin, dextrin, dextran, levan, sialic acid and acetylglucosamine as well as oligosaccharides such as, but not limited to, fructooligosaccharides, galactooligosaccharides and soybean oligosaccharides.
- yeast extracts such as glycogen, glucose, fructose, rhamnose, lactulose, methyl- ⁇ -D-mannoside, p-nitrophenol- ⁇ -D-mannoside, maltose, maltodextrin, dextrin, dextran, levan, sialic acid and acety
- Fiber or fermentable substrates such as psyllium may be used in the present compositions as may gums such as guar gum and xanthum gum.
- 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 ⁇ -glycerophosphates are also useful as growth factors.
- the growth factor is preferably selective for establishing and maintaining the growth of lactic acid bacteria, most preferably Lactobacillus and/or Bifidobacterium species. Growth factors preferable for use in the compositions of the present invention include lactose, lactulose, rhamnose, oligosaccharides and glycogen. Mixtures of these nutrients may also be used.
- the growth factor of the present invention is an oligosaccharide such as, but not limited to, galactooligosaccharides, soybean oligosaccharides and fructooligosaccharides. Oligosaccharides 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.
- oligosaccharide such as, but not limited to, galactooligosaccharides, soybean oligosaccharides and fructooligosaccharides. Oligosaccharides
- 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.
- 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
- Growth factors are preferably inco ⁇ orated 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.
- Coating Material The compositions of the present invention may further comprise a coating material.
- Coating materials useful to the compositions of the present invention may be water soluble as well as water insoluble.
- the coating material of the present invention is preferably dried to a water activity (A w ) of less than about 0.6, more preferably less than about 0 45, most preferably less than about 0.3.
- water activity is well known in the art as the measure of the ratio of the equilibrium vapor pressure of water above a substance such as food (solid or liquid) to the vapor pressure of pure water, both taken at the same temperature. A more detailed description of water activity is found in U.K. Patent 2,014,429.
- Water soluble coatings useful to the compositions of the present invention may include sugar or organic coatings.
- Sugar coatings useful to the present compositions may be syrupy materials containing monosaccharides or polymers of two or more saccharide units.
- Organic coatings are also useful to the compositions of the present invention.
- Useful organic polymers or copolymers used include those having a plurality of carboxylic acid and ester groups. Such groups are largely responsible for physical or chemical interactions with an active ingredient for effective taste masking properties.
- the preferred polymers or copolymers contain either a vinyl and acrylic acid and/or ester groups or carboxylic acid and/or ester groups. The specific polymers/copolymers are readily ascertained by one of ordinary skill in the art.
- polymers/copolymers that are pharmaceutically acceptable in terms of safety and toxicity may be used. It is preferred that such polymers copolymers be soluble in a solvent or a mixture of solvents
- Such polymers/copolymers include polymeric or resinous substances such as co-polymers of acrylic and substituted acrylic acids, cellulose esters, vinyl and substituted vinyl esters, polysulfonic acids, their esters and amides
- Specific examples include naturally occurring materials such as shellac and zein and synthetic and semi-synthetic materials such as ethyl cellulose, cellulose acetates, cellulose acetate phthallates, ethyl vinyl acetates and/or phthalates, polyvinyl acetates and/or phthalates, ethyl and/or methyl methacrylic acids, esters and co-polymers, hydroxy alkyl cellulose acetates and/or phthalates
- Such compounds include commercially available materials sold under trade names such as Eudragit S
- One particular embodiment of the present invention comprises a core containing at least one species of the Ericaceae family and a coating material containing a viable culture of at least one species of the above described microencapsulated bacteria
- the microencapsulated Lactobacillus can reside in the core coated with a coating material containing the Ericaceae species The latter may find use in providing an acidic environment for the Lactobacillus to survive and grow Additional coating layers may also be added.
- Protein-like coating components may 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-vahne (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
- a tablet coating materials are zeolites and clays to make tablets more palatable Zeolites have found use as bacterial feed coatings for domestic animals
- tiamulin 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
- the sugar and/or organic coatings of the present invention may be applied by conventional means including mechanical methods such as pan coating, air suspension techniques, multiorifice centrifugal techniques and spray drying techniques as well as physicochemical methods such as coacervation-phase separation. Coating procedures are more fully discussed in Remington's Pharmaceutical Sciences (Alfonso Gennarol, editor), 1666-1675 (1990), herein inco ⁇ orated by reference. Buffering Agents The compositions of the present invention may also contain a buffering agent.
- buffering agents suitable for use in the compositions of the present invention are those capable of maintaining a urogenital pH of about 3 0 to about 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).
- 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 inco ⁇ orated into the compositions of the present invention. Such plants or extracts include echinacea, allium, bucha, juniper ginseng, allicin, chlorella, algin and the like. Mixtures of these additional plants or extracts may also be used.
- Nutritional additives may also be inco ⁇ orated 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, minerals, amino acids such as glycine, phytochemicals and mixtures thereof. These additives may, alternatively, be first inco ⁇ orated into the Lactobacillus and/or Bifidobacterium of the present invention.
- Pharmaceutical Actives include, but are not limited to, proteins and carbohydrates other than those mentioned herein as growth factors, vitamins, minerals, amino acids such as glycine, phytochemicals and mixtures thereof.
- 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.
- appropriate measures should be taken to avoid contact with the microorganisms of the present invention. Such measures may include, but are not limited to, modifying the microencapsulation process as suggested by U.S. Patent 5,466,463 to Ford .
- analgesics preferred for use in the present invention include acetaminophen, acetyl salicylic acid, indomethacin and optically active isomers or racemates of ibuprofen, naproxen, flurbiprofen, carprofen, tiaprofenic acid, cicloprofen, ketoprofen, ketorolac, etodolac, indomethacin, sulindac, fenoprofen, diclofenac, piroxicam, benzydomine, nabumetone, their pharmaceutically acceptable salts and mixtures thereof.
- 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 including atropine, clidinium and dicyclomine; antacids including aluminum hydroxide, bismuth subsalicylate, bismuth subcitrate, simethi
- compositions of the present invention may be inco ⁇ orated are many and varied and depend largely upon the end use of the compositions. These carriers are pharmaceutically acceptable and 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.
- compatible 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 or viability of the compositions under ordinary use situa ⁇ tions.
- 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.
- 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, gels, liniments, oils and ointments, douches.
- Creams, gels and other base formulations may be used in topical administration of the present compositions to, for example, male or female genitalia (including the vulva and vagina) 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.
- compositions of the present invention may also be incorporated 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.
- 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 inco ⁇ orating the present compositions are described in U.S. Patent 4,891,227 to Thaman et al., herein inco ⁇ orated 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 purified water.
- 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. However, such liquid forms may require special care where free water is present with the Lactobacillus to prevent fermentation or degradation of the Lactobacillus.
- compositions can also contain wetting agents, emulsifying agents, suspending agents, as well as additional therapeutic actives
- wetting agents emulsifying agents
- suspending agents emulsifying agents
- additional therapeutic actives emulsifying agents
- Tablets can be compressed, molded, triturated, enteric-coated, sugar-coated, film- coated or multiple compressed, containing suitable binders, lubricants, diluents, disintegrating agents, and flow-inducing agents.
- 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 inco ⁇ orated to produce a gelatin shell
- Useful plasticizers of the present invention include glycerin, sorbitan, sorbitol, or similar low molecular weight polyols, and mixtures thereof.
- compositions of the present invention may be achieved by inco ⁇ orating 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%.
- 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 compositions, 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 inco ⁇ orated by reference
- 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
- Lactobacillus and/or Bifidobacterium species cultures can be freeze dried (or purchased freeze dried)
- an inoculum of Lactobacillus and/or Bifidobacterium is grown in a sterile nutrient media (e g Trypticase Soy agar broth). The media is removed by centrifugation The bacteria isolates are washed using a sterile balanced salt and 5% glucose solution The bacteria are then "snap frozen" with liquid nitrogen and vacuum freeze dried The freeze dried product is then checked for bacterial plate count and then diluted so that the plate count per unit dose composition is from about IO 3 to about IO 12
- the freshly obtained, washed and lyophilized bacteria obtained as described above are suspended in 10 ml of 5% glucose saline solution in such volume so as to obtain a heavy suspension of bacteria which contains between one to 10 ⁇ organisms per ml, at 0-
- the gelled droplets or little spheres are further washed with at least a five fold excess of the 0.1% CHES 1.1% calcium chloride, and normal saline solution
- the resultant spheres are then "snap frozen" in liquid nitrogen and then lyophilized After these steps, the encapsulated organisms can be used in the formulations of the present invention.
- Example III A tablet form of the present invention is made by combining the following components using conventional mixing and tableting technology
- the cranberry extract is granulated with half the Avicel and the K2932 in ethanol
- the granulation is then passed through a 12 mesh screen and dried at 120°F
- the dried granulation mixture is passed through a 20 mesh screen
- To the sieved granulation is added the -lactobacillus, remaining Avicel, Explotab and talc and mixed until uniform.
- Magnesium stearate is then added to the uniform mixture with mixing.
- the resultant granulation mixture is then compressed using conventional tableting processes.
- Example IV A oral capsule form of the present invention is made by combining the following components using conventional mixing technology. Ingredient % Weight
- Example V A topical gel form of the present invention is made by combining the following components using conventional mixing technology. Ingredient % Weight
- Water is added to a suitable size container. While mixing at a moderate speed (300 ⁇ m), the Poiyacrylamide and C13.J4 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 ⁇ ) until the cranberry extract and fructooligosaccharide are dissolved.
- the lactobacillus culture is added to the water phase and mixed at low speed ( 100 ⁇ m) until a uniform solution results
- the PPG- 14 Butyl ether is slowly added to the water phase to form a gel.
- the resulting gel is mixed at moderate speed until uniform
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Abstract
This application relates to compositions useful in preventing and/or treating urogenital and intestinal disorders, comprising an effective amount of at least one plant species of the Ericaceae family or its extract and a culture of at least one species of microencapsulated bacteria selected from the group consisting of lactobacillus, bifidobacterium and mixtures thereof.
Description
UROGENITAL AND INTESTINAL COMPOSITIONS
TECHNICAL FIELD This application relates to compositions useful in preventing and/or treating urogenital and intestinal disorders.
BACKGROUND OF THE INVENTION 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, klebsiella and clostridia, to the relatively nonpathogenic, such as lactobacillus and bifidobacterium. Deviations from this delicate flora 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 flora balance is, therefore, essential to maintaining optimal health.
One way of establishing or maintaining the body's flora is by administering lactobacillus. The use of lactobacillus to treat urogenital and intestinal disorders has been proposed, for instance, in Canadian Patent 1,298,556, issued April 4, 1992, to Bruce et al., PCT Application Serial Number WO 93/09793, published May 27, 1993, to Reid et al. and U.S. Patent 5,176,911, issued January 5, 1995, to Tosi et al. Researchers hypothesize that lactobacillus provide host protection via adherence to intestinal or vaginal epithelial cells.
Notwithstanding such proposals, several factors have been identified, casting doubt on the use of lactobacillus as single agent therapy for urogenital and/or gastrointestinal infection. 1) Variation exists among strains of lactobacillus concerning the degree to which individual strains of lactobacillus can adhere to epithelial surfaces. Reid, G. et al., Examination of strains of Lactobacillus for properties that may influence bacterial interference in the urinary tract. J. Urol., 138:330-335;1987. This variation may also extend to individual microorganisms. 2) Pathogenic microorganisms are most reliably excluded where lactobacillus colonies are established prior to pathogenic invasion. Hawthorn, L.A. et al., Exclusion of uropathogen adhesion to polymer surfaces by Lactobacillus acidophilus. Jour. Biomed. Mat. Res., 24;39-46; 1990; a nonexistent
situation, however, barring in vitro design. 3) Viability issues exist regarding orally ingested live bacterial cultures. Clinical research reveals that not all live bacteria survive the digestive fluids of the stomach and upper intestinal tract. Those which do survive may emerge too weak or too few in number to effectively colonize the lower intestine. Moreover, recognizing the need for sound clinical studies in the area, some researchers express further concern as to the efficacy of certain lactobacillus species. Therefore, despite the disclosures relating to lactobacillus products, there still remains a need for improved urogenital and gastrointestinal tract compositions incoφorating lactobacillus.
The present inventors have found that compositions incorporating plants or extracts of the Ericaceae family with microencapsulated Lactobacillus and/or
Bifidobacterium provide improved compositions for treating and/or preventing urogenital and gastrointestinal disorders by modifying the interaction of pathogens with cellular tissue. Recent studies also suggest the value of Ericaceae extracts in treating urinary tract infections. -Researchers have observed that various species of Vaccinium (e.g. cranberry and blueberry) contain a polymeric compound which 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
199I;324;1599. Suφrisingly, 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 to provide compositions for dietary supplementation.
Another object of the present invention is to provide improved compositions comprising a viable colony of microencapsulated lactobacillus and/or bifidobacteria.
A further object of the present invention is to provide compositions effective in preventing and/or treating urogenital and intestinal disorders. 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 methods for 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.) an antiadhesive amount of at least one plant species of the Ericaceae family or its extract; and
b.) a viable culture of at least one species of microencapsulated bacteria selected from the group consisting of lactobacillus, bifidobacterium and mixtures thereof The present invention also relates to the above compositions further comprising a growth factor for facilitating the growth of lactic acid bacteria.
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 phrase "antiadhesive amount," as used herein, means an amount effective to reduce the number of pathogenic microorganisms on the epithelial and/or mucosal lining of the urogenital and/or intestinal tract.
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. The term "nonpathogenic," as used herein, means substantially lacking the ability to cause disease or abnormality in healthy mammals. The term "healthy," as used herein, means free of underlying disease and/or immunosuppression
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 Plants or extracts of the Family Ericaceae The Ericaceae (heath) family, consisting of about 1 10 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 rsi). 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-resistent). 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 the adhesion of 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, issued December 12, 1995, to Walker et al., herein incoφorated 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 Ericaceae genera including, but not limited to, Vaccinium, Arctostaphylos, Gaultheria, and Gaylussacia. Preferred species include, V. australe, V. corymbosum, V. occidental, V. ova turn, V. myrtillus, V. parvifolium, V. uliginosum, V. macrocarpon, 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 1 Omg, 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 is 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. Species of Lactobacillus or Bifidobacterium
Another essential component of the present invention is a viable colony of microencapsulated 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. catenqforme, L. brevts, L. bulgancus, L. lactis, L. reuterii, L. gasseri, L helveticus, L. casei, L plantaru , L. delbruecku, L. thermop lis, L. jensenu, L crispatus, L. rogosae and L. fermentu 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. catenqforme, L. casei, L. crispatus, L. delbruecku, L. jensenu, 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 as core and/or coating components at levels of at least about 10^ cells per unit dose, preferably at levels of from about 10"* to about 1012 cells per unit dose and most preferably at levels of from about 10 > to about 10 *υ 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
The Lactobacillus and/or Bifidobacterium species of the present invention must also be microencapsulated. Viable Lactobacillus and/or Bifidobacterium bacteria that have been lyophilized after the removal of the growth media can be used for encapsulation The bacteria can be obtained from commercial sources, or can be obtained from laboratory strains. Suitable media include MRS, Thayer-Martin media, Trypticase Soy, Brain-Heart Infusion Broth, or any other enriched media suitable for the cultivation of these organisms, as no particular media is critical to the success of this suppository The only important factors are the viability and quantity of the micro-organisms that are always determined by standard clinical laboratory dilution methods, such as plating the quantified dilution of bacteria on to blood agar plates or other enriched media, incubating at 37°C for 24-48 hours in a 5-10% carbon dioxide atmosphere, and then performing a colony count The removal of the nutrient media is done by centrifugation at 14,000 x g at 0°-4°C, and then washing with sterile, balanced salts and 5% glucose solution at least three times after the initial centrifugation. The bacteria are then "snap frozen" with liquid nitrogen and then lyophilized under high vacuum The bacteria are then microencapsuled according to conventional microencapsulation technology. Suitable methods of encapsulation are disclosed in U.S. Patent 5.466.463. issued November 14, 1995, to Ford and U S Patent 5.407.609. issued April 18, 1995, to Tice, both of which are herein incoφorated by reference in their entirety. OPTIONAL COMPONENTS
Lactobacillus Growth Factor
Also useful to the compositions of the present invention is a growth factor for facilitating the growth of lactic acid bacteria. The phrase "a growth factor for facilitating the growth of lactic acid bacteria," as used herein is meant 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, 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 contain fermentable carbohydrate, peptone, meat and 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.
Examples of suitable growth factors include, but are not limited to, yeast extracts; gangliosides; salicin; mono-, di- and polysaccharide sugars such as glycogen, glucose, fructose, rhamnose, lactulose, methyl-α-D-mannoside, p-nitrophenol-α-D-mannoside, maltose, maltodextrin, dextrin, dextran, levan, sialic acid and acetylglucosamine as well as oligosaccharides such as, but not limited to, fructooligosaccharides, galactooligosaccharides and soybean oligosaccharides. Fiber or fermentable substrates such as psyllium may be used in the present compositions as may gums such as guar gum and xanthum gum. Similarly, 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 are also useful as growth factors. The growth factor is preferably selective for establishing and maintaining the growth of lactic acid bacteria, most preferably Lactobacillus and/or Bifidobacterium species. Growth factors preferable for use in the compositions of the present invention include lactose, lactulose, rhamnose, oligosaccharides and glycogen. Mixtures of these nutrients may also be used.
More preferably the growth factor of the present invention is an oligosaccharide such as, but not limited to, galactooligosaccharides, soybean oligosaccharides and fructooligosaccharides. Oligosaccharides 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 frutose 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. Coating Material The compositions of the present invention may further comprise a coating material.
Coating materials useful to the compositions of the present invention may be water soluble as well as water insoluble. The coating material of the present invention is preferably dried to a water activity (Aw) of less than about 0.6, more preferably less than about 0 45, most preferably less than about 0.3. The term "water activity," as used herein, is well known in the art as the measure of the ratio of the equilibrium vapor pressure of water above a substance such as food (solid or liquid) to the vapor pressure of pure water, both taken at the same temperature. A more detailed description of water activity is found in U.K. Patent 2,014,429.
Water soluble coatings useful to the compositions of the present invention may include sugar or organic coatings. Sugar coatings useful to the present compositions may be syrupy materials containing monosaccharides or polymers of two or more saccharide units. Organic coatings are also useful to the compositions of the present invention Useful organic polymers or copolymers used include those having a plurality of carboxylic acid and ester groups. Such groups are largely responsible for physical or chemical interactions with an active ingredient for effective taste masking properties. The preferred polymers or copolymers contain either a vinyl and acrylic acid and/or ester groups or carboxylic acid and/or ester groups. The specific polymers/copolymers are readily ascertained by one of ordinary skill in the art. Generally, polymers/copolymers that are pharmaceutically acceptable in terms of safety and toxicity may be used. It is preferred that such polymers copolymers be soluble in a solvent or a mixture of solvents Such
polymers/copolymers include polymeric or resinous substances such as co-polymers of acrylic and substituted acrylic acids, cellulose esters, vinyl and substituted vinyl esters, polysulfonic acids, their esters and amides Specific examples include naturally occurring materials such as shellac and zein and synthetic and semi-synthetic materials such as ethyl cellulose, cellulose acetates, cellulose acetate phthallates, ethyl vinyl acetates and/or phthalates, polyvinyl acetates and/or phthalates, ethyl and/or methyl methacrylic acids, esters and co-polymers, hydroxy alkyl cellulose acetates and/or phthalates Such compounds include commercially available materials sold under trade names such as Eudragit S (trademark of Rohm Pharma) and Phthalavin (trademark of Colorcon) The coating material of the present invention is preferably a polymeric mixture of methacrylic acid and methacrylate Mixtures of sugar and organic coating may also be used
One particular embodiment of the present invention comprises a core containing at least one species of the Ericaceae family and a coating material containing a viable culture of at least one species of the above described microencapsulated bacteria Alternatively, the microencapsulated Lactobacillus can reside in the core coated with a coating material containing the Ericaceae species The latter may find use in providing an acidic environment for the Lactobacillus to survive and grow Additional coating layers may also be added.
Additionally, Protein-like coating components may 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-vahne (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, tiamulin 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
The sugar and/or organic coatings of the present invention may be applied by conventional means including mechanical methods such as pan coating, air suspension techniques, multiorifice centrifugal techniques and spray drying techniques as well as
physicochemical methods such as coacervation-phase separation. Coating procedures are more fully discussed in Remington's Pharmaceutical Sciences (Alfonso Gennarol, editor), 1666-1675 (1990), herein incoφorated by reference. 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 about 3 0 to about 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, chlorella, algin 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, minerals, amino acids such as glycine, phytochemicals and mixtures thereof. These additives may, alternatively, be first incoφorated into the Lactobacillus and/or Bifidobacterium of the present invention. 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. When incoφorating pharmaceutical actives, appropriate measures should be taken to avoid contact with the microorganisms of
the present invention. Such measures may include, but are not limited to, modifying the microencapsulation process as suggested by U.S. Patent 5,466,463 to Ford.
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, carprofen, 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 incoφorated are many and varied and depend largely upon the end use of the compositions. These carriers are pharmaceutically acceptable and 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 or viability of the compositions under ordinary use situa¬ tions. 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, gels, liniments, oils and ointments, douches.
Creams, gels and other base formulations may be used in topical administration of the present compositions to, for example, male or female genitalia (including the vulva
and vagina) 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 incorporated 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 Thaman 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 purified 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. However, such liquid forms may require special care where free water is present with the Lactobacillus to prevent fermentation or degradation of the Lactobacillus. 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, enteric-coated, sugar-coated, film- coated or multiple compressed, containing suitable binders, lubricants, diluents, disintegrating agents, and flow-inducing agents.
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 incorporated 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 compositions, 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 incorporated 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 The Lactobacillus and/or Bifidobacterium species cultures can be freeze dried (or purchased freeze dried) To provide freeze dried cultures, an inoculum of Lactobacillus
and/or Bifidobacterium is grown in a sterile nutrient media (e g Trypticase Soy agar broth). The media is removed by centrifugation The bacteria isolates are washed using a sterile balanced salt and 5% glucose solution The bacteria are then "snap frozen" with liquid nitrogen and vacuum freeze dried The freeze dried product is then checked for bacterial plate count and then diluted so that the plate count per unit dose composition is from about IO3 to about IO12
Example II
The freshly obtained, washed and lyophilized bacteria obtained as described above are suspended in 10 ml of 5% glucose saline solution in such volume so as to obtain a heavy suspension of bacteria which contains between one to 10^ organisms per ml, at 0-
4°C All of these procedures are performed in the 0-4°C temperature range unless otherwise noted, in order to maintain viability of the lactobacilli bacteria which at room temperature lose viability The suspension of bacteria is rapidly, but gently, stirred while
0.2-0.4 ml of sodium alginate solution (1.5% weight by volume) is added The above mixture is then transferred into a 4 liter round bottom flask by using a nitrogen stream through a sheathed 14 gauge needle The 4 liter round bottom flask was previously washed with a 5% albumin solution, and thereafter heated for at least 10 hours at 65°C, and the needle and the tubing used in the process have also been treated this way
Thereafter the above mixture is forced through a 30 gauge multi-beveled needle under pressure using a large syringe and nitrogen stream Very small droplets are generated at the end of the needle which are dried by the nitrogen and air stream around the 30 gauge needle, and the droplets are collected in an aqueous solution of 1 3-2% calcium chloride where they gel Thereafter, they are washed at least three times with 0.08-0.13% 2-(N-cyclohexyl-amino) ethanesulfonic acid (CHES) solution and 1 0-1 5% calcium chloride solution.
The gelled droplets or little spheres are further washed with at least a five fold excess of the 0.1% CHES 1.1% calcium chloride, and normal saline solution The resultant spheres are then "snap frozen" in liquid nitrogen and then lyophilized After these steps, the encapsulated organisms can be used in the formulations of the present invention.
Example III 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 37 300%
Lactobacillus l 29 900%
K2932 (5% ethanol soln)2 13 4 00%
Avicel (pH 101)3 13 400%
Explotab4 1 8%
Talc 3 600%
Magnesium stearate 0 600%
1 Microencapsulated Lactobacillus Caseii var. rhamnosus (108 cfu/g)
2 Polyvinylpyrollidone TM for microcrystalline cellulose, a highly purified particulate form of cellulose ^ A brand of sodium starch glycolate
The cranberry extract is granulated with half the Avicel and the K2932 in ethanol The granulation is then passed through a 12 mesh screen and dried at 120°F The dried granulation mixture is passed through a 20 mesh screen To the sieved granulation is added the -lactobacillus, remaining Avicel, Explotab and talc and mixed until uniform. Magnesium stearate is then added to the uniform mixture with mixing. The resultant granulation mixture is then compressed using conventional tableting processes.
Example IV A oral capsule form of the present invention is made by combining the following components using conventional mixing technology. Ingredient % Weight
Concentrated Cranberry Extract 29.900%
Bifidobacterium1 15.000% fructooligosaccharide2 29.900%
Avicel3 22.400% Ac Di Sol4 2 800%
1 Microencapsulated Lactobacillus bifidus subsp pennsylvanicus ( 108 cfu/g). Available as NutraFlora FOS from Golden Technologies Company, Inc TM for microcrystalline cellulose, a highly purified particulate form of cellulose.
4 A brand of a cross-linked form of sodium carboxymethylcellulose. Combine and mix the cranberry extract, fructooligosaccharide, Lactobacillus culture, Avicel and Act 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 V 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% Lactobacillus1 2 50% fructooligosaccharide2 6 00% Poiyacrylamide and C \ 3. \ 4
Isoparaffin and Laureth-73 4 00% PPG- 14 Butylether 8.00% Water, Purified q.s
1 Microencapsulated Lactobacillus Caseii var. rhamnosus (108 cfu/g). 2 Available as NutraFlora FOS from Golden Technologies Company, Inc Available as Sepigel from Seppic Corporation
Water is added to a suitable size container. While mixing at a moderate speed (300 φm), the Poiyacrylamide and C13.J4 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 φ ) until the cranberry extract and fructooligosaccharide are dissolved. The lactobacillus culture is added to the water phase and mixed at low speed ( 100 φm) until a uniform solution results The PPG- 14 Butyl ether is slowly added to the water phase to form a gel. The resulting gel is mixed at moderate speed until uniform
Claims
WHAT IS CLAIMED IS
1 A composition for treating or preventing urogenital and intestinal disorders, comprising a ) an antiadhesive amount of at least one plant species of the Ericaceae family or its extract, and b ) a viable culture of at least one species of microencapsulated bacteria selected from the group consisting of lactobacillus, bifidobacteπum and mixtures thereof
2 A composition according to Claim 1, further comprising a growth factor wherein the growth factor is selected from the group consisting of lactulose, rhamnose, oligosaccharides, glycogen and mixtures thereof
3 A composition according to Claim 1 or 2, further comprising a coating material having an Aw of less than about 0 6 and having suspended therein the microencapsulated bacteria
4 A composition according to any one of the preceding Claims, further comprising a carrier selected from group consisting of suppository, tablet, troche, oral liquid, suspension, capsule, gelatin capsule
5 A composition according to any one of the preceding Claims, wherein the species of lactobacillus is selected from the group consisting of L. acidophilus, L. gasseri, L. catenaforme, L. casei, L. crispatus, L. delbruecku, L. jensenu, L rogosae, L. fermentum, L. plantarum and mixtures thereof and wherein the species of bacteπa is present at a level of IO4 to IO12 lactobacillus cells per unit dose of the composition, preferably 10^ to 10lυ lactobacillus cells per unit dose of the composition
6 A composition according to any one of the preceding Claims, wherein the plant or extract is a species selected from the genus Vaccinium
7 A composition according to any one of the preceding Claims, further comprising nutritional additives selected from the group consisting of vitamins, minerals,
amino acids, phytochemicals and mixtures thereof and/or an additional plant extract selected from the group consisting of echinacea, allium, bucha, juniper ginseng, allicin, chlorella, algin and mixtures thereof and/or a pharmaceutical active selected from the group of consisting of analgesics, gastrointestinal actives and mixtures thereof
A topically administered composition for treating or preventing urogenital disorders, comprising: a ) an antiadhesive amount of at least one plant species of the Ericaceae family or its extract; and b.) a viable culture of at least one species of microencapsulated bacteria selected from the group consisting of lactobacillus, bifidobacterium and mixtures thereof.
A composition according to Claim 8, further comprising an oligosaccharide growth factor selected from the group consisting of galactooligosaccharides, soybean oligosaccharides, fructooligosaccharides and mixtures thereof and/or a buffering agent selected from the group consisting of boric acid, hippuric acid, tartaric acid, sorbic acid, benzoic acid, lactic acid, ascorbic acid, citric acid, acetic acid, proprionic acid, pharmaceutically acceptable salts thereof and mixtures thereof
A composition according to Claim 8 or 9, further comprising a carrier selected from group consisting of suppository, vaginal tablet, vaginal gelatin capsules, vaginal troche, cream, gel, ointment, lotion, irrigant, douche, tissue, wipe, panty liner, feminine napkin, tampon, diaper and incontinent care product
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US601480 | 1984-04-18 | ||
US60148096A | 1996-02-14 | 1996-02-14 | |
PCT/US1997/001662 WO1997029762A1 (en) | 1996-02-14 | 1997-02-06 | Urogenital and intestinal compositions |
Publications (1)
Publication Number | Publication Date |
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EP0880354A1 true EP0880354A1 (en) | 1998-12-02 |
Family
ID=24407644
Family Applications (1)
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EP97904914A Withdrawn EP0880354A1 (en) | 1996-02-14 | 1997-02-06 | Urogenital and intestinal compositions |
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EP (1) | EP0880354A1 (en) |
JP (1) | JPH11504048A (en) |
CN (1) | CN1211188A (en) |
AU (1) | AU1758197A (en) |
CA (1) | CA2245810A1 (en) |
WO (1) | WO1997029762A1 (en) |
Families Citing this family (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999002042A2 (en) * | 1997-07-05 | 1999-01-21 | Societe Des Produits Nestle S.A. | Frozen dessert containing lactic bacteria and fermentable fibres |
PT1014969E (en) * | 1997-09-09 | 2009-02-17 | Univ Rutgers | Plant proanthocyanidin extract effective at inhibiting adherence of bacteria with p-type fimbriae to surfaces |
SE519648C2 (en) * | 1998-03-06 | 2003-03-25 | Essum Ab | New strain of Lactobacillus plantarum |
DK0956858T3 (en) * | 1998-04-30 | 2002-01-28 | Vesely Renata Maria Cavaliere | Pharmaceutical preparations containing lactobacilli for the treatment of vaginal infections |
US7767203B2 (en) | 1998-08-07 | 2010-08-03 | Ganeden Biotech, Inc. | Methods for the dietary management of irritable bowel syndrome and carbohydrate malabsorption |
US6461607B1 (en) * | 1998-08-24 | 2002-10-08 | Ganeden Biotech, Inc. | Probiotic, lactic acid-producing bacteria and uses thereof |
US6080401A (en) * | 1998-11-19 | 2000-06-27 | Reddy; Malireddy S. | Herbal and pharmaceutical drugs enhanced with probiotics |
EP1189521B1 (en) * | 1999-03-05 | 2006-10-25 | Shanbrom Technologies, LLC | Soluble plant derived natural color concentrates and antimicrobial nutraceuticals |
WO2000071138A2 (en) * | 1999-05-25 | 2000-11-30 | Gregor Reid | Oral administration of lactobacillus for the maintenance of health in women |
IT1306716B1 (en) * | 1999-06-21 | 2001-10-02 | Mendes S U R L | ASSOCIATION OF LACTIC BACTERIA AND ITS USE FOR THE PREVENTION AND / OR THERAPEUTIC TREATMENT OF INFECTIONS AND INFLAMMATORY STATES. |
JP4603116B2 (en) * | 1999-12-02 | 2010-12-22 | わかもと製薬株式会社 | Lactic acid bacteria-containing composition, medicine and food |
SE518097C2 (en) | 2000-10-03 | 2002-08-27 | Ellen Ab | Process for the preparation of an absorbent sanitary article comprising lactic acid producing bacteria as well as such |
GB2369777B (en) * | 2000-10-05 | 2004-10-27 | St Ivel Ltd | Food products with antimicrobial lactic acid bacteria |
FI109602B (en) | 2001-01-25 | 2002-09-13 | Valio Oy | Probiotkombination |
EP1228769A1 (en) * | 2001-02-02 | 2002-08-07 | Jörg-Peter Prof. Schür | Symbiotic regenerative composition |
FR2827774B1 (en) * | 2001-07-30 | 2005-06-24 | Dolisos Lab | PHARMACEUTICAL AND / OR DIETARY PREPARATIONS CONTAINING ACTIVE PLANT VEGETABLE EXTRACT AND PROBIOTIC MICROORGANISMS |
SE0104199L (en) * | 2001-12-13 | 2003-06-14 | Sca Hygiene Prod Ab | New product |
US20030143262A1 (en) | 2001-12-13 | 2003-07-31 | Brusk Ulla Forsgren | Hygiene tissue |
DE60323734D1 (en) * | 2002-03-21 | 2008-11-06 | Bifodan As | Lactobacillus strains |
US20030229335A1 (en) * | 2002-04-30 | 2003-12-11 | Payne Richard Grady | Apparatus and method for delivery of constrained beneficial bacteria to the vaginal tract |
US7785640B2 (en) * | 2004-01-16 | 2010-08-31 | Amerilab Technologies, Inc. | Effervescent composition including cranberry extract |
GB0410785D0 (en) * | 2004-05-14 | 2004-06-16 | Glycologic Ltd | Improved prebiotic |
FR2874826B1 (en) * | 2004-09-08 | 2006-12-22 | Pharmatoka Soc Par Actions Sim | NEW SURGICAL AND / OR MEDICAL DEVICES AND THEIR USE |
FR2875406B1 (en) * | 2004-09-21 | 2007-01-05 | Danisco | STRAIN OF LACTOBACILLUS ACIDOPHILUS HAVING ANALGESIC PROPERTIES AT THE GASTROINTESTINAL SYSTEM LEVEL |
EP1965839B1 (en) | 2005-12-22 | 2012-07-25 | SCA Hygiene Products AB | Absorbent article |
JP2009521254A (en) * | 2005-12-22 | 2009-06-04 | エスセーアー・ハイジーン・プロダクツ・アーベー | Absorbing material |
EP3628164A1 (en) | 2007-08-29 | 2020-04-01 | Ganeden Biotech, Inc. | Baked goods |
CN101642189B (en) * | 2008-08-07 | 2012-05-30 | 北京大北农科技集团股份有限公司 | Microcapsule compound feed additive and preparation method thereof |
BRPI0919651A2 (en) | 2008-10-16 | 2015-08-18 | Ganeden Biotech Inc | Grain-based probiotic compositions |
EP2210505A1 (en) * | 2009-01-27 | 2010-07-28 | Nestec S.A. | Composition comprising caftaric acid and/or derivatives thereof |
EP2424550B1 (en) | 2009-04-29 | 2017-06-07 | Ganeden Biotech, Inc. | Bacterial cell membrane formulation |
IT1403661B1 (en) * | 2011-01-28 | 2013-10-31 | Probiotical Spa | EFFERVESCENT COMPOSITION IN THE SOLID FORM FOR USE IN VAGINAL APPLICATIONS FOR THE TREATMENT OF VAGINAL INFECTIONS. |
WO2012135499A1 (en) | 2011-03-31 | 2012-10-04 | Ganeden Biotech, Inc. | Probiotic sports nutrition compositions |
ITMI20110793A1 (en) | 2011-05-09 | 2012-11-10 | Probiotical Spa | STRAINS OF PROBIOTIC BACTERIA AND SYNBIOTIC COMPOSITION CONTAINING THEMSELVES INTENDED FOR THE BABY FOOD. |
ITMI20110791A1 (en) | 2011-05-09 | 2012-11-10 | Probiotical Spa | BACTERIA OF BACTERIA ABLE TO METABOLIZE THE OXALATES. |
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. |
ITRM20110477A1 (en) | 2011-09-09 | 2013-03-10 | Giovanni Mogna | COMPOSITION INCLUDING N-ACETYLCISTEIN AND / OR LYSOZYME MICROINCAPSULATE GASTROPROTECT IN ASSOCIATION WITH PROBIOTIC BACTERES ABLE TO RESTORE THE BARRIER EFFECT OF THE STOMACH THAT IS LOST DURING THE PHARMACOLOGICAL TREATMENT OF |
ITMI20111718A1 (en) | 2011-09-23 | 2013-03-24 | Probiotical Spa | A WATERPROOF MOISTURE AND OXYGEN MATERIAL FOR PACKAGING DIETARY, COSMETIC AND MEDICINAL PRODUCTS. |
US9987222B2 (en) | 2012-01-31 | 2018-06-05 | Biosoma B.V. | Method for administration of a probiotic |
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. |
MX2016014991A (en) * | 2014-05-16 | 2017-09-11 | Pizeta Group Srl | Compositions containing boric acid and a mixture of lactobacillus. |
KR102587444B1 (en) | 2015-09-29 | 2023-10-11 | 킴벌리-클라크 월드와이드, 인크. | Synergistic composition to maintain a healthy balance of microflora |
JP7118594B2 (en) * | 2016-03-31 | 2022-08-16 | 小林製薬株式会社 | antidiarrheal composition |
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 |
US10258567B1 (en) | 2016-11-17 | 2019-04-16 | Grace Procurements Llc | Vaginal probiotic products and related processes |
RU2748651C2 (en) | 2017-02-28 | 2021-05-28 | Кимберли-Кларк Ворлдвайд, Инк. | Synergic composition to maintain healthy balance of microflora |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2421066A1 (en) * | 1974-05-02 | 1976-03-25 | Solco Basel Ag | Bifido bacterial preparations - additionally contg. Lactobacillus casei var. rhamnosus |
SE446940B (en) * | 1983-02-16 | 1986-10-20 | Carl Axel Virdalm | MEASURES FOR FIGHTING DISEASE CONDITIONS IN THE FOOD MELTER CONTAINING SHALL OR OUTSIDE OF BEERS OR FRUITS |
DE3404474A1 (en) * | 1983-04-06 | 1984-10-11 | James Gorden Belleair Fla. Roberts | METHOD FOR PRODUCING A MULTIPLE FERMENTED DAIRY PRODUCT |
IT1227154B (en) * | 1988-08-05 | 1991-03-19 | A Tosi Farmaceutici S R L Nova | PHARMACEUTICAL COMPOSITIONS FOR GYNECOLOGICAL USE BASED ON LATTOBACILLI |
US5219842A (en) * | 1989-08-29 | 1993-06-15 | Nihon Shokuhin Kako Co., Ltd. | Method of improving intestinal floras |
GB2261372A (en) * | 1991-11-15 | 1993-05-19 | Gregor Reid | Lactobacillus and skim milk compositions for prevention of urogenital infection |
US5525341A (en) * | 1992-10-09 | 1996-06-11 | Jlb, Inc. | Partially purified cranberry anti-adhesion activity |
US5474774A (en) * | 1994-03-25 | 1995-12-12 | Jlb, Inc. | Adhesion inhibiting composition |
-
1997
- 1997-02-06 WO PCT/US1997/001662 patent/WO1997029762A1/en not_active Application Discontinuation
- 1997-02-06 CA CA002245810A patent/CA2245810A1/en not_active Abandoned
- 1997-02-06 EP EP97904914A patent/EP0880354A1/en not_active Withdrawn
- 1997-02-06 AU AU17581/97A patent/AU1758197A/en not_active Abandoned
- 1997-02-06 JP JP9529373A patent/JPH11504048A/en active Pending
- 1997-02-06 CN CN97192254A patent/CN1211188A/en active Pending
Non-Patent Citations (1)
Title |
---|
See references of WO9729762A1 * |
Also Published As
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CN1211188A (en) | 1999-03-17 |
JPH11504048A (en) | 1999-04-06 |
AU1758197A (en) | 1997-09-02 |
CA2245810A1 (en) | 1997-08-21 |
WO1997029762A1 (en) | 1997-08-21 |
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