U.S. patent application number 09/726753 was filed with the patent office on 2001-04-05 for symptomatic relief of allergic reactions.
Invention is credited to Keller, Robert H., Wen, Xue-Lan.
Application Number | 20010000144 09/726753 |
Document ID | / |
Family ID | 22232818 |
Filed Date | 2001-04-05 |
United States Patent
Application |
20010000144 |
Kind Code |
A1 |
Keller, Robert H. ; et
al. |
April 5, 2001 |
Symptomatic relief of allergic reactions
Abstract
The composition disclosed is a unique formulation of Traditional
Chinese Medicine (TCM) extracts created to reduce the debilitating
symptoms of allergies. It combines a number of organically grown,
but, non-organically extracted, standardized formulations of
natural ingredients which have been used singly for hundreds of
years for symptomatic relief of allergies. These include Ginseng
and Gan Cao, which provide a natural anti-inflammatory effect; Bai
Gao, which prevent the smooth muscle spasms associated with
allergic reactions; Suan Zao ren, which provides an antihistamine
effect without the usual sedative effect; and Wu Mai, which reduces
the local swelling associated with allergies. Combined, it was
unexpectedly found that these ingredients provide a natural,
non-drying, non-sedating alternative to antihistamines, without
inhibiting the natural healing mechanisms.
Inventors: |
Keller, Robert H.; (Weston,
FL) ; Wen, Xue-Lan; (Miami, FL) |
Correspondence
Address: |
Ronald R. Santucci
Pitney, Hardin, Kipp & Szuch, LLP
20th Floor
711 Third Avenue
New York
NY
10017
US
|
Family ID: |
22232818 |
Appl. No.: |
09/726753 |
Filed: |
November 30, 2000 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09726753 |
Nov 30, 2000 |
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09349100 |
Jul 8, 1999 |
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6180106 |
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60092352 |
Jul 10, 1998 |
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Current U.S.
Class: |
424/728 ;
424/725; 424/752; 424/757 |
Current CPC
Class: |
A61K 36/16 20130101;
A61K 36/258 20130101; A61K 36/725 20130101; A61K 36/48 20130101;
A61K 36/725 20130101; A61K 36/48 20130101; A61K 36/16 20130101;
A61K 36/736 20130101; A61K 36/736 20130101; A61K 2300/00 20130101;
A61K 36/258 20130101; A61K 2300/00 20130101; A61K 2300/00 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101 |
Class at
Publication: |
424/728 ;
424/752; 424/757; 424/725 |
International
Class: |
A61K 035/78 |
Claims
CLAIMS
1. A composition of matter, which comprises in admixture, the
following ingredients: ginseng root; gingko biloba leaf; Ziziphus
seed; mume fruit; licorice root.
2. The composition of claim 1 wherein the composition comprises at
least 3% of each of the ingredients.
3. The composition of claim 1 where the composition comprises at
least 10% of each of the following ingredients: mume fruit and
licorice root.
4. The composition of claim 1 further comprising flavorants.
5. The composition of claim 1 further comprising a pharmaceutically
acceptable carrier.
6. The systemic administration of a pharmaceutically effective
amount of the composition according to claim 1, 2 or 3 to a mammal
suffering a type I hypersensitivity reaction to an allergen, for
the relief of symptoms associate with the reaction.
7. The systemic administration of a pharmaceutically effective
amount of the composition according to claim 2 to a mammal
suffering a type I hypersensitivity reaction to an allergen, for
the relief of symptoms associate with the reaction.
8. The systemic administration of a pharmaceutically effective
amount of the composition according to claim 3 to a mammal
suffering a type I hypersensitivity reaction to an allergen, for
the relief of symptoms associate with the reaction.
9. The systemic administration of a pharmaceutically effective
amount of the composition according to claim 1 to a mammal to act
as a cough suppressant.
10. The systemic administration of a pharmaceutically effective
amount of the composition according to claim 1 to a mammal to
suppress itching.
11. The topical administration of a pharmaceutically effective
amount of the composition with a pharmaceutically acceptable
carrier according to claim 1 to a mammal to suppress itching.
12. The systemic administration of a pharmaceutically effective
amount of the composition according to claim 1 to a mammal to act
as an antihistamine.
13. The systemic administration of a pharmaceutically effective
amount of the composition according to claim 1 to a mammal to act
as an anti-inflammatory.
14. Administration according to claim 1 wherein a pharmaceutically
effective is 0.1 mg/kg to about 50 mg/kg of body weight of the
mammal, daily.
15. Administration according to claim 1 wherein a pharmaceutically
effective is 0.5 mg/kg to about 25 mg/kg of body weight of the
mammal, daily.
Description
BACKGROUND OF THE INVENTION
1. 1. Field of the Invention
2. This invention relates to pharmaceutical compositions and
methods for the treatment of mammals suffering symptoms of allergic
reactions.
3. 2. Brief Description of Related Art
4. An allergy is defined as an immune response in a mammal induced
by an environmental antigen that has deleterious effects resulting
in significant tissue damage and inflammation. Allergies comprise
one of the most common medical problems in the twentieth century
with some estimates suggesting that as many at 10% of the
population may be affected. The antigen (allergen) is a
non-parasitic antigen and the immune response is generally a type I
hypersensitivity reaction. This reaction, which comprises mast cell
or basophil degranulation manifests itself clinically in disorders
related to biological effects of mediators released by the
degranulation. These mediators are pharmacologically active agents
that act on local tissues to increase vascular permeability and
inflammation. Primary mediators such as histamine, serotonin,
protease, prostaglandins SRS-A and similar substances released
during degranulation may actually be more detrimental than
beneficial to the comfort and well-being of the affected
individual. the biological effects are the symptoms of the
hypersensitivity reactions.
5. The classical treatment of type I hypersensitivity reactions has
heretofore comprised administration of, for example, antihistamines
or a process termed desensitization. Desensitization involves
multiple injections and requires frequent visits to a doctor over a
long period of time. Antihistamines are, of course, effective to
relieve the symptoms associated with the type I hypersensitivity
reaction. Antihistamine treatment suffers from problems including
drying of the mucous membranes and sedation as well as manifest
side effects of depression and drowsiness. In addition,
antihistamines can interact with other medicines. Warnings are
given to refrain from operating machinery when antihistamines are
administered. Both methods are expensive.
6. Ideally, the treatment of the symptoms associated with allergic
hypersensitivity reactions avoids the administration of
antihistamines or blocks the other mediators in the allergic
cascade causing a reduction in the symptoms.
7. It has been observed that traditional Chinese pharmacopoeia
includes medicinals which have been time-tested for safety and
effectiveness. For example, ginseng has been used in China for over
5,000 years. In a traditional Chinese medical context, ginseng is a
"tonic" or "adaptogen" considered by many to be a substance which
is not harmful and causes minimal changes or symptoms in the
physiological functions of an organism. This herbal root is used
throughout Asia to promote an overall sense of well being, stamina
and strength. In this regard, it is believed by many that ginseng
preparations act to modulate stress, replenish vital energy,
improve performances under a wide variety of stressful conditions,
increase blood volume, promote appetite, quiet the spirit and
provide wisdom. It is, in fact, listed in the Merck Index as
therapeutically an "aromatic bitter".
8. However, even in traditional Chinese medicine ginseng is not
considered a panacea. The general practioner, after determining a
diagnosis and before prescribing medication, will map a course of
treatment strategy. When he prescribes medication, including
ginseng, he will always prescribe the ginseng in combination with
some other remedy which, depending on the diagnosis, will operate
in the same direction or in the opposite direction to bring the yin
and yang into balance, even though the condition under treatment
may respond to administration of ginseng alone.
SUMMARY OF THE INVENTION
9. The invention comprises a composition for oral or local
administration to a mammal suffering a type I hypersensitivity
reaction to an allergen, for the relief of symptoms associated with
the reaction, which comprises; in admixture, particlized
10. ginseng root;
11. ginko biloba leaf;
12. Ziziphus seed;
13. mume fruit; and
14. licorice root.
15. The invention also comprises a method for the symptomatic
relief of a type I hypersensitivity reaction in a mammal, which
comprises orally administering to said mammal an effective dose for
said relief, of a mixture of ginseng root, ginko biloba leaf,
Ziziphus seed, mume fruit and licorice root.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE
INVENTION
16. Those skilled in the art will gain an appreciation of the
invention from the following discussion of the preferred
embodiments of the invention.
17. Ginseng (called "renshen" in Chinese) is the root of a
botanical, found naturally in China and Korea. The best known
ginseng on a worldwide basis is Asian ginseng (Panax ginseng),
which is also widely cultivated in the United States. There are
other varieties, such as Siberian ginseng (Eleutheroccus
senticosus). The root comprises resin, panaxatriol and other
substances containing a steroid nucleus, sugar, starch, mucilage, a
saponin, volatile oil or triterpenoid glycosides including, in
particular, P. quinquefolium and P. pseudoginseng which are
generally considered to be biologically active. Isolation and
identification of ginseng saponins is described in Kaku et al.,
Arzneimittel-Forsch. 25, 343 (1975). Use in oriental medicine as
tonic: K. Chimin Wong, Wu Lien-the, History of Chinese Medicine
(Shanghai, 2nd ed., 1936) 906 pp. Comprehensive review of
morphology, cultivation and uses appears in Baranov, Econ. Bot. 20,
403-406 (1966).
18. As a therapeutic composition, Ginseng is classified as an
aromatic bitter; Merck Index, No. 4256. It has a sweet, aromatic
taste which can be referred to as "exotic".
19. Research suggests to some that ginseng has nonspecific
immunostimulatory activity similar to that of the herb
Echinacea.
20. The present invention does not make any claim for curative
benefit from the use of ginseng, but suggests that its inclusion in
the composition of the invention has accepted advantages, including
but not limited to at least some of the advantages mentioned
above.
21. Dried ginseng root is generally administered to adults in doses
of 2 to 8 grams per day (when used singly).
22. The leaf of the Ginkgo biloba tree is rich in flavonoid
glycosides content along with ginkogolides and bilbalides. Ginkgo
biloba is a chemical mediator of allergic symptoms in the group of
substances termed leukotrienes. Although these chemicals are
partially inhibited by licorice, they are more completely inhibited
by Ginkgo. As such, these herbs in combination serve to more
effectively block the inflammatory component of allergies by
inhibiting the effects of multiple inflammatory mediators. Extracts
of the leaf (24% extract) are commercially available from a number
of providers (for example, Boehringer Ingelheim Pharmaceuticals,
Inc., Ridgefield, Conn.) who manufacture a standardized 24 percent
extract. The extract (Chinese name: bai goo) has been identified as
a mild sedative which prevents smooth muscle spasms associated with
type I hypersensitivity reactions. The herb is also a stimulant to
the circulatory system. The dosage administered to adults is
generally within the range of 40 to 120 mg/per day (when used
singly).
23. The seed of Ziziphus jujuba (Rhamnaceae) known in China as suan
zao ren provides an antihistamine effect without the usual sedative
side effect. This herb acts as a general calmer to the immune
system without compromising its ability to defend us from bacteria,
viruses etc. Suan zao ren functions in allergic reactions to
decrease the levels of symptoms by decreasing immune chemicals. In
addition, it contains Vitamin C which also has been shown to be
protective in allergic conditions. It may be administered to adults
in a dosage of from 6 to 15 gms/day (used singly). The Chinese use
this medication to calm the nerves and relax the body.
24. Commonly called licorice root, the root of Glycyrrhiza
uralensis (leguminosae) known also as "gan cao" or Chinese licorice
is used in Chinese medicine to slow and prolong the effect of
strong tonics. In combination with the ginseng it functions to
provide a prolonged anti-inflammatory effect. It is generally
administered to adults in a dosage of 2 to 10 grams/day (when used
singly). Equivalent sources of glycyrrhiza are the root of G.
glabra L. variety typica (Spanish licorice) and other varieties
containing 6-14 percent of glycyrrhizn (the glucoside of
glycyrrhetic acid). Inflammation is a central phenomenon associated
with all allergic reactions and the reason that allergic symptoms
are frequently treated with local steroids as well as
antihistamines. Licorice provides a natural alternative and in
conjunction with Ginseng provides both a significant anti-
inflammatory as well as an antihistamine effect. In addition, it
provides a natural suppressant for the coughs that commonly
accompany allergic reactions.
25. The unripened, dried fruit of the tree Prunus mume known as
"black-plums" and known in China ss wu mei, is possessive of
astringent properties. This traditional Chinese herb has a variety
of effects. In the context of allergies, however, it has both a
direct antihistaminic effect as well as preventing the vascular
leakiness associated with sever allergies. The mechanism by which
this occurs remains obscure. When used in the present invention at
a dosage of 100 to 600 mg per day, the ingredient functions to
reduce local swelling, of tissues, associated with the type I
hypersensitivity reaction.
26. The ingredients described above in combination, work
synergistically to provide the necessary action required for
response to type I hypersensitivity reaction to an allergen, while
supporting the mammal's ability to heal itself since administration
of the combination does not inhibit natural tissue repair
mechanisms. The ingredients work together to calm the biochemical
triggers and clinical symptoms of allergies without the expense and
inconvenience of desensitization or the sedating and drying effects
of antihistamines. This gains importance as allergic symptoms
(which result from the release of chemicals from the surface of
basophils and mast cells) are caused not only by histamine but by a
variety of chemicals. As a result, antihistamines, the most
commonly used anti-allergy therapy, cannot totally block symptoms
as they do not prevent the actions of other released chemicals.
27. As each of these ingredients has properties which enhances the
properties of the others, it is preferable that there be at least
3% of each of the ingredients in the compound. In more preferred
embodiments, there is at least 10% of each of the following
ingredients: Ziziphus seed; mume fruit; and licorice root. It will
be appreciated that the proportion of the ingredients may be
adjusted to address the individual needs of patients depending on
the severity of the various symptoms of allergies such as sneezing,
coughing, stuffy nose, headaches, nausea, itching, and various
other associated symptoms.
28. Clinical Testing
29. The efficacy of the compound has been demonstrated in clinical
tests. Ten patients were on a treatment of prescription
antihistamines (sold under the trademarks Claritin.RTM. or
Zyrtec.RTM.) for a period of 6 to 8 months. Then the patients were
taken off the prescription antihistamines and instead given a two
dosage units twice a day (as described in Example 1 below) of the
inventive compound for a period of 6-9 months. FIG. 1 shows a graph
which indicates that the IgE level (which is a standard measure of
the presence of allergen) in patients taking the inventive compound
was significantly reduced (by 3563) after a patient is given
Applicant's inventive compound when compared with patients the
traditional antihistamine where the reduction was 1275. This
demonstrates that the inventive compound is almost three times as
effective in reducing allergies as currently prescribed commercial
brands.
30. This invention also relates to pharmaceutical dosage unit forms
for systemic administration (oral) which are useful in treating
mammals, including humans to relieve the symptoms of a type I
allergic reaction. The term "dosage unit form" as used in this
specification and in the claims refers to physically discrete units
suitable as unitary dosage for mammalian subjects, each unit
containing a predetermined quantity of the essential active
ingredient; calculated to produce the desired effect in combination
with the required pharmaceutical means which adapt said ingredient
for systemic administration. Examples of dosage unit forms in
accordance with this invention are tablets, capsules, orally
administered liquid preparations in liquid vehicles and dry
preparations for the extemporaneous preparation of preparations in
a liquid vehicle. Solid diluents or carriers for the solid oral
pharmaceutical dosage unit forms are selected from the group
consisting of lipids, carbohydrates, proteins and mineral solids,
for example, starch, sucrose, kaolin, dicalcium phosphate, gelatin,
acacia, corn syrup, corn starch, talc and the like. Capsules, both
hard and soft, are formulated with conventional diluents and
excipients, for example, edible oils, talc, calcium carbonate,
calcium stearate, magnesium stearate and the like. Liquid
pharmaceutical preparations for oral administration may be prepared
in water or aqueous solutions which advantageously contain
suspending agents, such as for example, sodium
carboxymethylcellulose, methylcellulose, acacia, polyvinyl
pyrrolidone, polyvinyl alcohol and the like. Such preparations must
be stable under the conditions of manufacture and storage, and
ordinarily contain in addition to the basic solvent or suspending
liquid, preservatives in the nature of bactericidal and fungicidal
agents, for example, parabens, chlorobutanol, benzyl alcohol,
phenol, thimerosal, and the like. In many cases it is preferable to
include isotonic agents, for example, sugars or sodium chloride.
Carriers and vehicles include vegetable oils, water, ethanol, and
polyols, for example, glycerol, propylene glycol, liquid
polyethylene glycol, and the like.
31. The pharmaceutical dosage unit forms are prepared in accordance
with the preceding general description to provide an effective
amount of the essential active ingredient per dosage unit form in
admixture with the means for adaptation to systemic administration.
In general, the unit dose form will contain 5 to 95 percent by
weight of the essential active ingredient.
32. It is also contemplated that the composition may be applied
topically to relieve allergic reactions which manifest itself in
the form an itch. Suitable vehicles to act as a pharmaceutically
acceptable carriers for topical administration are found in U.S.
Pat. Nos. 5,916,905 and 5,902,827 incorporated herein by reference
and are known to those skilled in the art.
33. It will be appreciated that the exact dosage of the essential
active ingredient constituting an effective amount for treatment of
a mammal according to the method of the invention will vary greatly
depending on the specific nature of the clinical condition being
treated, severity of the condition, species of mammal; age, weight
and condition of the mammal and the specific formulation being
administered. The exact dose required for a given situation may be
determined by administration of a trial dose and observation of the
clinical response. In general, an effective amount to be
administered will be within a range of from about 0.1 mg. per kg.
to about 50 mg. per kg. of body weight of the recipient, daily.
Preferably 0.5 mg./kg. to about 25 mg./kg. daily is provided. In
most instances. In cases such as the treatment of hay fever, it may
be desirable to repeat the administrations several times daily over
periods of time.
34. The following examples and preparations describe the manner and
process of making and using the invention and set forth the best
mode contemplated by the inventor of carrying out the invention but
are not to be construed as limiting.
EXAMPLE 1
35. A mixture of the following ingredients is prepared by hand
mixing:
1 English Name Chinese Name Source Amount Ginseng 20% ren shen root
100 mg Ginko biloba 24% bai gao leaves 30 mg Ziziphus suan zao ren
seed 20 mg Mume Fruit wu mei fruit 100 mg Licorice Root gan cao
root 50 mg
36. The mixture which constitutes the essential active ingredient
of the composition of the invention, may be compounded into wafers,
tablets or capsules containing 330 to 500 mg of active ingredient.
In an uncompounded form, the mixture may be orally administered to
an adult human 1 to 4 times a day or as recommended by a health
care professional. Alternatively, the mixture may be mixed with
juice, water or food to facilitate oral administration.
EXAMPLE 2
37. Three thousand tablets for oral use, each containing 330 to 500
mg of essential active ingredient are prepared from the following
ingredients:
2 essential active ingredient (Example 1) 1500 g starch (Rx-1500)
300 g magnesium stearate, USP 39 g colloidal silicic acid 19.5 g
Avicel .RTM. pH 102. q.s. to 3900 g
38. The essential active ingredient is ground through a 0.25 mm
sieve opening screen. The powdered active ingredient, with 50% of
the total amount of magnesium stearate be used, colloidal silicic
acid and Avicel.RTM. pH 10.2 are passed through a 40 mesh sieve,
mixed for 20 minutes and then slugged. The slugs are broken down by
forcing through a screen No. 11, and mixed with the remaining
magnesium stearate and compressed into tablets.
39. One tablet given orally 1 to 4 times a day is useful in the
relief of symptoms of inflammation in adult humans provoked by
allergic response , or like etiological causes.
EXAMPLE 3
40. Three thousand capsules for oral use, each containing 330 to
500 mg of the essential active ingredient, from Example 1, supra.,
are prepared from the following ingredients:
3 essential active ingredient (Example 1) 330-500 g colloidal
silicic acid 30 g magnesium stearate, USP 30 g microcrystalline
cellulose 150 g lactose 90 g
41. In accordance with the active ingredient potency, the amount of
lactose is adjusted to achieve a weight of 900 mg for each capsule.
The ingredients are passed through a 40 mesh sieve and mixed for 30
minutes. Hard gelatin capsules No. 0 are filled using Zanazi, model
RV-59 equipment. The capsules are preserved in airtight,
light-resistant containers. For adults, a suggested use: Take 1 to
2 capsules, two times daily during the allergy season, as a dietary
supplement or as directed by a health case practitioner.
* * * * *