Chemistry: analytical and immunological testing – Biological cellular material tested
Reexamination Certificate
1999-08-31
2001-06-19
Wallenhorst, Maureen M. (Department: 1743)
Chemistry: analytical and immunological testing
Biological cellular material tested
C436S164000, C435S004000, C435S029000
Reexamination Certificate
active
06248591
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to in vitro methods for evaluating the safety of whole herb extracts for parenteral use by examination of blood cells and plasma after exposing them to various concentrations of extracts with high-resolution phase-contrast microscopy.
BACKGROUND OF THE INVENTION
A large number of pharmacologic agents are derived from plant sources. The traditional approach to preparation of such pharmaceutical agents employs fractionation of natural, plant-derived substances into their individual bioactive components followed by chemical characterization of one or more fractions for use as single drugs. While this approach has yielded a rich formulary of potent drugs for managing acute disorders, the long-term effects of such drugs carry significant potential for adverse effects. The use of whole herb extracts, by contrast, are generally not as potent as plant-derived drugs. This has been validated by empirical observations with combinations of herbs formulated to restore altered bowel, blood, liver, and other body organ ecosystems (A. Majid, J. Integrative Medicine 2:4-55, 1988; A. Majid, “The Cortical Monkey and Healing”, pp. The Institute of Preventive Medicine, Bloomfield, N.J. 1989; A. Majid, “The Cortical Monkey and Healing”, pp. 73-75, Institute of Preventive Medicine, Bloomfield, N.J. 1990; and A. Majid, “Healing, Miracles and the Bite of the Gray Dog”, Life Span, Denville, N.J. 1997). It seems likely that such safety follows use of a large number of herbs in smaller amounts. Beyond that, there is the important issue of plant substances carrying their own “counteracting” components that neutralize some of the toxicity of individual and highly concentrated fractions such as those used in plant-derived drugs. Thus, highly purified plant fractions (drugs), while effective in acute illnesses, may not be optimal for use for slow and sustained reparative work for damaged body organ ecosystems.
Herbs have been used for medicinal uses by the oral route for hundreds of years (Theophrastus (370-285 BC), “Enquiry into Plants”, in 2 vols., translated by A. Hort, W. Heinmann, London, 1916; “Herbs, Spices, and Medicinal Plants: Recent Advances in Botany, Horticulture, and Pharmacology”, Lyle E. Cracker and James E. Sinom, eds, Oryx Press, Phoenix, Ariz., Vol. 1, 1986; “Folk Medicine: The Art and the Science”, Richard P. Steiner, Ed., American Chemical Society, Washington, D.C., 1986, ISBN-0-8412-0939-1; J. A. Duke, “CRC Handbook for Medicinal Herbs”, CRC Press, Boca Raton, Fla. 1985). Injectable extracts of individual compounds derived from plant sources, such as colchicine, have been used for their medicinal values for decades in many countries. The Chinese have clinically used extracts of whole herbs with increasing frequency during the last few decades. It is known that certain herbs, when administered intramuscularly, produce results that contrast with those empirically observed with oral use (J. A. Duke, “The Green Pharmacy”, Rodale Press, Emmanus, Pa. 1997, ISBN-0-87596-316-1). One possible explanation for that phenomenon may be that active ingredients of such herbs undergo conformational changes when they are subjected to the normal digestive/absorptive processes after oral administration.
The potential clinical benefits of parenteral use of mixtures of whole herb extracts need to be explored for several reasons. First, extensive empirical experience indicates that injectable forms of many therapeutic agents are far more effective than the preparations for oral use. Empirical experience with mixture of injectable herb extracts, though limited, suggests the possibility that the clinical outcome with the use of injectable extracts may be improved. Second, there is the potential of injectable herbal mixtures providing greater benefits just as oral herbal mixtures give superior results than the use of single herbs. Third, there are many anecdotal reports of control of malignant neoplasms and other serious autoimmune disorders with injectable herbal mixtures for which there are no effective drug therapies. However, details of such therapies are rarely published, and the safety of their use cannot be assumed.
The clinical safety of herbs, in general, has been established by empirical use by herbologists and integrative physicians. A central issue in parenteral use of herbal formulations, however, is the potential danger of serious hemolytic and nonhemolytic reactions when they are given parenterally. Specifically, there is the issue of phytoagglutinins, natural plant-derived substances with ability to bind a large variety of cell membrane ligands, causing serious hemolytic and nonhemolytic reactions (D. L. J. Freed, “Dietary Lectins and disease”, In: Food Allergy and Intolerance, J. Brostoff and S. J. Challacombe, Eds., 1987, Bailliere Tindal, East Sussex, England; P. Ganguly et al., Biochim. Biophys. Acta 627:256-261, 1980; I. hilgert et al., Nature 284:273-275, 1980). An example of a highly toxic phytoagglutinin is that derived from beans of the castor plant. Even commonly ingested wheat germ agglutinins are known to cause agglutinin reactions in certain individuals (D. L. J. Freed, “Dietary Lectins and disease”, In: Food Allergy and Intolerance, J. Brostoff and S. J. Challacombe, Eds., 1987, Bailliere Tindal, East Sussex, England). Accordingly, there is a need for evaluating the safety of whole herb extracts for parenteral use.
SUMMARY OF THE INVENTION
It is, therefore an object of the invention to provide an vitro method for evaluating the safety of whole herbal extracts.
In one embodiment, the present invention provides a method of evaluating the safety of a herbal extract for parenteral use comprising: (a) contacting blood cells with the extract; and (b) examining the blood cells for at least one membrane deformity.
In another embodiment the present invention provides a method of evaluating the safety of a herbal extract for parenteral use comprising: (a) contacting plasma with the extract; and (b) examining the plasma for formation of a condition selected from the group consisting of zones of congealing, microclots and microplaques.
Other objects and advantages of the present invention will become apparent from the following description and appended claims.
DETAILED DESCRIPTION OF THE INVENTION
It has now been found that the objectives of this invention are realized by employing in vitro microscopic methods for direct assessment of the immediate and delayed effects of contacting blood cells and plasma components with whole herb extracts. The blood cells are examined for membrane deformities. Preferably, the blood cells examined are erythrocytes. Also preferably, the membrane deformity is selected from the group consisting of loss of normal plasticity, wrinkling, and agglutination. When the plasma is contacted with the herbal extract, it is examined for formation of a condition selected from the group consisting of zones of congealing, microclots and microplaques.
While these morphological changes in the cells can occur after exposure to any concentration of herbal extract, the majority of these changes (75% or more, preferably 90% and more preferably 95%) are reversible after a period of time ranging from 15 minutes to one hour. In this case, these concentrations are safe for parenteral use. On the other hand, if these morphological changes are permanent, then the blood cells with the morphological changes are presumed to be senescent or unhealthy as previously described (J. Integrative Medicine, 2:4-55, 1998). Accordingly, adverse side effects would be expected to be associated with parenteral administration of the concentration of herbal extract that causes the significant permanent morphological changes in blood cells and/or plasma.
In practicing the methods of the present invention, it is preferred to contact the blood cells or the plasma with different dilutions of the herbal extract in order to determine the safe concentration of the extract when administered parenterally. The effects of the herbal extracts on blood cells and plasma
Ostrolenk Faber Gerb & Soffen, LLP
Wallenhorst Maureen M.
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