Title:  Composition and method for the treatment of diaper rash using natural products

United States Patent:  6,419,963

Inventors:  Niazi; Sarfaraz K (20 Riverside Dr., Deerfield, IL 60015)

Appl. No.:  681520

Filed:  April 22, 2001

Provided here is a pharmaceutical composition containing beeswax, olive oil, .beta.-sitosterol and the herb Coptis chinesis Franch for safe and quick treatment for infant and adult diaper rash. Also provided here is a methodology for the treatment of diaper rash wherein the treatment consists of compositions that contain naturally derived anti-inflammatory agents, an antimicrobial agents and such components that they provide an occlusive coating when applied to the afflicted surface.

DETAILED DESCRIPTION OF THE INVENTION

In this invention, we have discovered that the ideal treatment for diaper rash is to provide a combination of components that have diversified activity. We have found that the natural composition described below provides an optimal and safe modality for the treatment of all types of diaper rashes as defined and described above.

A typical formulation of our invention includes all natural ingredients. It contains 2-20% beeswax, olive oil, soybean oil extract foro.1-50% .beta.-sitosterol and 1-50% of the herb Coptis chinensis Franch. A preferred embodiment includes the following composition: Coptis chinensis Franch, 5% (as an extract) .beta.-sitosterol 0.5% (from soybean extract), Beeswax 8%, Olive Oil qs.

Coptis chinensis Franch used in the invention is selected but not limited to one or more from the group of Coptis deltoidea C. Y. Cheng et Hsiao, Coptis omeiensis (Chen) C. Y. Cheng, and Coptis teetoides C. Y. Cheng of Ranunculaceae Family. The root is used. (A Dictionary of Chinese Materia Medica, Shanghai Science and Technology Press, 1988, pages 2022 to 2030). The primary components include: berberine, coptisine, worenine, palamtine, jatrorrhizine, epiberberine, magnoflorine, and columbamine. It has a very broad spectrum antibacterial property against gram-positive and gram-negative pathogens such as alpha and beta hemolytic streptococci, staphylococcus aureus, virbio cholerae, diplococcus intracellularis, diplococcus pneumoniae, bacillus anthracis, bacillus tetani, diptheria bacillus, tuberculosis bacillus, E coli. It also inhibits leptospira. A remarkable effect of huanglian is that it enhances the phagocytic activities of leukocytes and liver reticuloendothelial system. It also acts as vasodilator.

A large volume of scientific literature establishes the safe antibacterial and other pharmacological properties of Coptis chinensis Franch as shown below.

Qin C L, Liu J Y, Cheng Z M: Pharmacological studies on the effects of huanglian decoction on experimental gastric lesions in rats and antiemetic in pigeons. Chung Kuo Chung Yao Tsa Chih July 1994; 19(7):427-30, 448. The results showed that Huanglian decoction has protective effect on ethanol-, HCl- and aspirin-induced gastric hemorrhagic lesions in rats and antemetic effect on CuSO4-induced vomiting in pigeons. A dose of 27 g/(kg.d) po applied in mice showed no toxic action. This dose is 400 times that of clinical application.

Franzblau SG, Cross C: Comparative in vitro antimicrobial activity of Chinese medicinal herbs.J Ethnopharmacol March 1986; 15(3): 279-88. Eighteen herbs used in the treatment of infectious diseases in traditional Chinese medicine were evaluated for in vitro activity against ten microbial pathogens. Lyophilized teas were tested by the agar dilution technique at 100-1600 micrograms/ml. Eleven of the preparations were active against at least one microorganism and six of these were active against at least three of the test isolates. Huangqin (Scutellaria sp.) and Huanglian (Coptis sp.) were each active against five of the isolates. Huangqin inhibited Klebsiella pneumoniae and Proteus vulgaris at 200 micrograms/ml. Huangqin alone showed strong activity against Mycobacterium smegmatis (less than or equal to 100 micrograms/ml) and Candida albicans (200 micrograms/ml). The antimicrobial activity of various teas, prepared with equal weights of herbs, could be compared against a particular pathogen by considering both the percentage of water-soluble material in the herbs and the minimum inhibitory concentrations of the filtered, lyophilized decoctions.

The choice of Coptis chinensis is made here as a potent antimicrobial agent. It does not contain any antibiotics to which patients can get resistant to, nor does it contain any irritating chemicals that might exacerbate the inflammation of skin. There are, however, other naturally derived components that possess antimicrobial activity against the type of organisms that infect during the formation of diaper rash. These may be substituted for Coptis chinensis. One may also use a combination of such herbs.

The major pharmacological effects of .beta.-sitosterol are anti-inflammation, antiulcer, promotion of injured tissue and as we have demonstrated, stimulation of basal dermal stem cell cells. Soybean extract containing a minimum of 40% .beta.-sitosterol as used in this invention (Sigma Chemicals Catalog S5753), which also contains campesterol, dihydro-brassicacasterol prepared according to the method of N. Kozumi, et al., Chem. Pharm. Bull., 27: 38, 1979. The source of .beta.-sitosterol however is not relevant. It could be obtained from natural sources or from synthetic sources. .beta.-sitosterol (C₂₉ H₅₀ O, molecular weight 414.72) is a common sterol in plants. It is generally isolated from wheat germ, soybean or corn oil. Sterols are important cyclized triterpenoids that perform many critical functions in cells. Phytosterols such as campesterol, stigmasterol and .beta.-sitosterol in plants, ergosterol in fungi and cholesterol in animals are each primary components of the cellular and sub-cellular membranes in their respective cell types. The dietary source of phytosterols in humans comes from vegetables and plant oils. The estimated daily phytosterol content in the conventional western-type diet is approximately 250 mg in contrast to a vegetable diet, which would provide double that amount. Although having no nutritional value to humans, phytosterols have recently received a great deal of attention due to their possible anti-cancer properties and their ability to decrease cholesterol levels when fed to a number of mammalian species, including humans. Phytosterols aid in limiting cholesterol absorption, enhance biliary cholesterol excretion and shift cholesterol from atherosclerotic plaque. While many of the mechanisms of action remain unknown, the relationship between cholesterol and phytosterols is apparent. This is perhaps not surprising given that chemically, phytosterols closely resemble cholesterol in structure. The major phytosterols are .beta.-sitosterol, campesterol and stigmasterol. Others include stigmastanol (.beta.-sitostanol), sitostanol, desmosterol, chalinasterol, poriferasterol, clionasterol and brassicasterol. (Gould R. G., Jones R. J., LeRoyu G. V., Wissler R. W., Taylor C. B.; Absorbability of .beta.-sitosterol in humans; Metabolism, (August) 1969;18 (8): 652-662; Tabata T., Tanaka M., Lio T.; Hypocholesterolemic activity of phytosterol. II; Yakugaku Zasshi, 1980;100 (5): 546-552. Hepistall R. H., Porter K. A.; The effect of .beta.-sitosterol on cholesterol-induced atheroma in rabbits with high blood pressure; Br. J. Experimental Pathology, 1957;38: 49-54.) Several novel applications of phytosterols including .beta.-sitosterol have been reported. The U.S. Pat. No. 5,965,449 to Novak describes a method of assessing risk for cardiovascular disease and other disorders and phytosterol-based compositions useful in preventing and treating cardiovascular disease and other disorders. The level of serum campesterol and .beta.-sitosterol are determined and their ratio is correlated with the risk of cardiovascular or a related disorder. The U.S. Pat. No. 5,523,087 to Shlyankevich is for a pharmaceutical composition for the treatment of diabetic male sexual dysfunction; it contains physosterogens, phosphatidyl choline, .beta.-sitosterol, Damiana leaf extract and vitamins and minerals. The U.S. Pat. No. 5,486,510 to Bouic, et al., is for a mixture of .beta.-sitosterol glucoside and .beta.-sitosterol is administered to persons for the modulation or control of immune responses. The U.S. Pat. No. 5,747,464 to See is for a composition for inhibiting absorption of fat and cholesterol from the gut and a method for making and using the composition. The composition comprises .beta.-sitosterol bound irreversibly to pectin to form a .beta.-sitosterol and pectin complex. The U.S. Pat. No. 5,118,671 to Bombardelli, et al., is for complexes formed between aescin, cholesterol or .beta.-sitosterol and phospholipids and a method for producing an anti-inflammatory effect is also described.

Natural beeswax contains many still yet unidentified components that have for centuries provided healing properties for many ailments. Propolis is just one such example. The isolation of D-002 series of alcohols provides the clue to its anti-inflammatory activity; flavolins and other minor components provide impart many pharmacologic properties to beeswax. In addition to its chemical and pharmacological characteristics, the natural crystalline structure of beeswax allows formation of a matrix structure when mixed with vegetable oils in specific proportions that further act to remove skin debris.

A large volume of published data attests to the therapeutic activity of beeswax.

Carbajal D, Molina V, Valdes S, Arruzazabala M L, Mas R, Magraner J: Anti-inflammatory activity of D-002: an active product isolated from beeswax.

Prostaglandins Leukot Essent Fatty Acids October 1998; 59 (4): 235-8. D-002 is a natural mixture of high molecular weight alcohols isolated and purified from beeswax, which contains triacontanol among its main components. This study was undertaken to investigate the anti-inflammatory effects of D-002 administered by the oral route in two animal models commonly used in the pharmacological screening of anti-inflammatory drugs. D-002 administered orally to rats (100 and 200 mg/kg) produced a mild but significant reduction of exudate volume in carrageenan-induced pleuritic inflammation that was accompanied by a marked and significant decrease of leukotriene B4 (LTB4) levels in the exudate. D-002 (25, 50 and 200 mg/kg) also significantly diminished the granuloma weight in the cotton pellet granuloma in rats. In both cases, D-002 was less effective than indomethacin, which was used as an established anti-inflammatory reference drug. On the other hand, D-002 administered from 25-1000 mg/kg did not induce erosions or gastromucosal lesions in rats, which differs from results usually obtained with non-steroidal anti-inflammatory drugs. These results indicate that D-002 is a mild anti-inflammatory agent without any ulcerogenic effect associated. The results suggest that these effects are probably not mediated through an inhibition of cyclooxygenase, but a reduction in LTB4 levels induced by D-002 could explain these results.

Carbajal D, Molina V, Valdes S, Arruzazabala L, Mas R: Anti-ulcer activity of higher primary alcohols of beeswax. J Pharm Pharmacol September 1995; 47 (9): 731-3. The anti-ulcer effects of a natural mixture of higher aliphatic primary alcohols, designated D-002, isolated from beeswax, were compared with those of cimetidine on indomethacin-, ethanol-, water-immersion-induced ulcers and on gastric secretion in rats. D-002 (25-50 mg kg-1 p.o.) was similar to cimetidine in dose-dependently reducing the duration of indomethacin-induced ulcers while also being effective in preventing ethanol-induced ulcers, which are not affected by cimetidine. On the other hand, D-002 (100 mg kg-1) moderately decreased the volume of gastric basal secretion in pylorus-ligated rats, but not the acidity. Nevertheless, it inhibited gastric ulcer induced by pylorus-ligation at doses (50 mg kg-1) that were ineffective in decreasing the volume. In addition, 100 mg kg-1 of D-002 prevented the formation of acute gastric ulcers induced in rats by water-immersion stress. The results demonstrate the anti-ulcer activity of the preparation in different experimental models suggesting its potential value for ulcer therapy.

Carbajal D, Molina V, Valdes S, Arruzazabala M L, Mas R, Magraner J: Anti-inflammatory activity of D-002: an active product isolated from beeswax.Prostaglandins Leukot Essent Fatty Acids October 1998;59(4):235-8. D-002 is a natural mixture of high molecular weight alcohols isolated and purified from beeswax, which contains triacontanol among its main components. This study was undertaken to investigate the anti-inflammatory effects of D-002 administered by the oral route in two animal models commonly used in the pharmacological screening of anti-inflammatory drugs. D-002 administered orally to rats (100 and 200 mg/kg) produced a mild but significant reduction of exudate volume in carrageenan-induced pleuritic inflammation that was accompanied by a marked and significant decrease of leukotriene B4 (LTB4) levels in the exudate. D-002 (25, 50 and 200 mg/kg) also significantly diminished the granuloma weight in the cotton pellet granuloma in rats. In both cases, D-002 was less effective than indomethacin, which was used as an established anti-inflammatory reference drug. On the other hand, D-002 administered from 25-1000 mg/kg did not induce erosions or gastromucosal lesions in rats, which differs from results usually obtained with non-steroidal anti-inflammatory drugs. These results indicate that D-002 is a mild anti-inflammatory agent without any ulcerogenic effect associated. The results suggest that these effects are probably not mediated through an inhibition of cyclooxygenase, but a reduction in LTB4 levels induced by D-002 could explain these results.

Liu F, Sun D: Active constituents lowering blood-lipid in beeswax. Zhongguo Zhong Yao Za Zhi September 1996;21(9):553-4, 576. Three compounds were isolated from the active fraction Lowering blood-lipid in the traditional Chinese beeswax (Apis cerana or A. mellifera). They were identified as dotriacontanol, triacontanol and octacosanol by chemical and spectroscopic methods.

Carbajal D, Molina V, Valdes S, Arruzazabala L, Rodeiro I, Mas R, Magraner J: Possible cytoprotective mechanism in rats of D-002, an anti-ulcerogenic product isolated from beeswax. J Pharm Pharmacol August 1996;48(8):858-60. D-002 is an anti-ulcerogenic product, isolated from beeswax, which consists of a well-defined mixture of higher primary aliphatic alcohols. It is highly effective against ethanolinduced ulcers. This study was designed to determine if D-002 shows cytoprotective properties on gastric mucosa in ethanol-induced ulcers. The involvement of endogenous prostaglandins in the protective effect of D-002 was also investigated. When a subulcerogenic dose of indomethacin (10 mg kg-1) was injected simultaneously with oral administration of ethanol, oral pre-treatment with D-002 (5-100 mg kg-1) partially inhibited the gastric protection. D-002 (5 and 25 mg kg-1) administered to normal rats significantly increased the soluble mucus content and also prevented its reduction in rats with ethanol-induced ulcers. In addition, D-002 administered at 5 and 25 mg kg-1 prevented the increase of vascular permeability induced by ethanol (60%) and reduced the concentration of thromboxane B2 (TXB2) in gastric mucosa of rats with ethanol-induced ulcers. These results support the hypothesis that the anti-ulcerogenic properties of D-002 could be related to a cytoprotective mechanism.

Dorset DL: The crystal structure of waxes. Acta Crystallogr B Dec. 1, 1995;51 (Pt 6): 1021-8. Quantitative electron crystallographic studies have been carried out on epitaxially oriented multi-component waxes. Intensities from two paraffin-based samples, an artificial six-component medium wax (equimolar distribution of chain lengths) and a petroleum-based wax (Gaussian distribution of chain lengths) have been used to determine their crystal structures. As found earlier for binary paraffin solid solutions, differences in molecular volume are compensated by longitudinal molecular shifts within individual lamellae. Nevertheless, each lamellar surface must remain flat enough, and with enough crystallographic order intact, to nucleate the next lamella, thus accounting for the observed long-range correlation in these crystals. Recrystallized beeswax also has a layer packing somewhat similar to the paraffin waxes. However, in this case, the lamellar order is `frustrated` so that a certain amount of `nematically` ordered material must be present, spanning the nascent lamellar interfaces.

Carbajal D, Molina V, Valdes S, Arruzazabala L, Mas R: Anti-ulcer activity of higher primary alcohols of beeswax. J Pharm Pharmacol September 1995;47(9):731-3. The anti-ulcer effects of a natural mixture of higher aliphatic primary alcohols, designated D-002, isolated from beeswax, were compared with those of cimetidine on indomethacin-, ethanol-, water-immersion-induced ulcers and on gastric secretion in rats. D-002 (25-50 mg kg-1 p.o.) was similar to cimetidine in dose-dependently reducing the duration of indomethacin-induced ulcers while also being effective in preventing ethanol-induced ulcers, which are not affected by cimetidine. On the other hand, D-002 (100 mg kg-1) moderately decreased the volume of gastric basal secretion in pylorus-ligated rats, but not the acidity. Nevertheless, it inhibited gastric ulcer induced by pylorus-ligation at doses (50 mg kg-1) that were ineffective in decreasing the volume. In addition, 100 mg kg-1 of D-002 prevented the formation of acute gastric ulcers induced in rats by waterimmersion stress. The results demonstrate the anti-ulcer activity of the preparation in different experimental models suggesting its potential value for ulcer therapy.

Zanoschi C, Ciobanu C, Verbuta A, Frincu D: The efficiency of some natural drugs in the treatment of burns. Rev Med Chir Soc Med Nat lasi January 1991-June 1995(1-2):63-5. In this paper we present an original product for burns. It is an ointment with bacteriostatic, bactericidal and epithelializing action and it is make up in accordance with technology of sunflower oil, beeswax, sintopholin, chloramphenicol, procaine, and vitamin E. An experimental study on burnt animals in order to prove the efficiency of the product was carried out. For histological investigation tegument was collected from the burnt area. A rapid evolution of epithelialization was found in case of treated animals as distinguished from control sample, where the infected crust was far from being healed. We also present some photos in account with the upper fact.

Ludianskii E A: The use of the products of bee raising in medicine. Feldsher Akush September 1989;54(9):36-9.

Blum M S, Jones T H, Rinderer T E, Sylvester H A: Oxygenated compounds in beeswax: identification and possible significance. Comp Biochem Physiol B 1988;91 (3):581-3.1. Beeswax synthesized by non-foraging honeybee workers contains six oxygenated volatiles in addition to a series of normal alkanes. 2. Decanal constitutes nearly 50% of the oxygenated volatiles and is accompanied by octanal, nonanal, furfural, benzaldehyde and 1-decanol. 3. The possible significance of the aldehydes as stimulators of hoarding behaviour and attractants for wax moths is discussed.

Chlorazak T, Szaflarski J, Seferowicz E, Scheller S: Preliminary evaluation of clinical usefulness of propolis (beeswax) preparations. Przegl Lek 1971;28 (12):828-31.

Olive oil used in the formulation provides several functions. It is an excellent emollient and through its many other components, complements the overall activity of the product. Olive Oil is a complex compound made of fatty acids, vitamins, volatile components, water-soluble components and microscopic bits of olive. Primary fatty acids are Oleic and linoleic acid. It also contains Vitamin E and carotene. Other constituents of olive oil include: phenols, free fatty acids, triacylglycerols, diacylglycerols, and monoacylglycerols, thiobarbituric acid, Pheophytin A andetc. The flavonoid polyphenols in olive oil are natural anti-oxidants, which have been shown to have a host of beneficial effects from healing sunburn to lowering cholesterol, blood pressure, and risk of coronary disease.There are as many as 5 mg of antioxidant polyphenols in every 10 grams of olive oil. Many other nut and seed oils have no polyphenols.

Claim 1 of 10 Claims

What is claimed is:

1. A pharmaceutical composition for the treatment of diaper rash consisting essentially of beeswax, olive oil, .beta.-sitosterol and the herb Coptis chinensis Franch.
 

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