EP1067947A1

EP1067947A1 - Use of extracts of echinacea pallida and echinacea angustifolia, dandelion (taraxacum) and plantain (plantago)

Info

Publication number: EP1067947A1
Application number: EP99917908A
Authority: EP
Inventors: Michel O. Ruepp
Original assignee: Individual
Current assignee: Individual
Priority date: 1998-04-02
Filing date: 1999-03-26
Publication date: 2001-01-17
Also published as: WO1999051250A1; AU3602199A; DE19814725A1

Abstract

The invention relates particularly to the use of extracts of Echinacea pallida (EP) and Echinacea angustifolia (EA), dandelion (Taraxacum, TA) and plantain (Plantago, PL), especially dry extracts from the fresh or dried plants, to produce medicaments for treating or preventing (protecting against) damage caused to organs and tissue by radiation (radioprevention, radioprotection), infection (infection prophylaxis) and chemical action (chemoprevention, chemoprotection), especially damage to the O-MALT system of the small bowel (inflammatory diseases, enteritis regionalis Crohn), the lungs (inflammation, disease), the bronchial tubes and the rhinopharynx (rhino-pharyngo-bronchitis, rhinitis, pharyngitis, sinusitis), the bone marrow (aplasia of the bone marrow), the thymus (dysfunction, aplasia or hypoplasia resulting from damage caused by medicaments or radiation) and the liver (atrophy, necrosis), for treating/preventing hepatitis A, B and C, for damage to the pancreas, insufficiency of the exocrine, secretory functions of proteases, esterases, carbohydrases and nucleases and impairment of the carbohydrate metabolism (Langerhans' islands), damage to the kidneys (insufficiency), and generally immunosuppressed conditions, for cellular immunostimulation, for treating leucocytopenia, granulocytopenia, lymphoctopenia, thrombocytopenia, erythrocytopenia (infect anaemia, tumour anaemia i.a.), immunoglobulin deficiency conditions, and for conditions resulting from AIDS, tumours and diseases with a suppressed immune system.

Description

USE OF ECHINACEA-PALLIDA AND ECHINACEA ANGUSTIFOLIA EXTRACTS; Dandelion (Taraxacum) extracts; SPITZWEGERICH-

(PLANTAGO) EXTRACTS

The invention relates to the use of Echinacea pallida and Echinacea angustifolia extracts, dandelion (Taraxacum) extracts, ribwort (Plantago) extracts, optionally in combination with artichoke (Cynara) extracts and / or nettle (Urtica) ) Extracts, in particular dry extracts, also in combination with other phytopharmaceuticals and / or chemically defined medicaments for the production of medicaments and for use in the context of high-dose phytopharmaceutical therapy.

E. pallida and E. angustifolia are very closely related. The composite specialist Cronquist regards E. angustifolia as a geographical variant of E. pallida. Our own in-vivo studies show that the orally administered extract of E. angustifolia and E. pallida is bioequivalent.

The use of extracts from Echinacea species for the prophylaxis and therapy of mild and moderate colds, flu infections and septic processes can be traced back to the successful treatment of purulent wounds and snake bites by the indigenous people of North America. From tradition it is known that the North American Indians used the roots of Echinacea angustifolia and Echinacea pallida: - for bacterial infections such as mumps, smallpox, measles, fever, bronchitis, sore throat, eye infection - for viral infections as an antidote to snake bites and insect bites.

The Indians obviously already knew the right raw material selection and dosage of the active ingredient. For internal application, the Echinacea roots were applied by chewing the root. "The Choctaws use it be chewing and swallowing the salvia. They keep a small piece of the root in the mouth nearly all the time, continuing the use for a long time" (Hopps, CR, 1989). This - 2 -

The method of application made success in the treatment of viral and bacterial diseases possible.

The white settlers of North America also used Echinacea species as a kind of "omnia sanans" (panacea), for example in saddle wounds. They also target them against bacterial infections such as: - sore throat, diphtheria, meningitis, cholera, smallpox, syphilis, and typhoid

Sepsis and against viral infections such as: - measles, rabies as well as herpes.

In the late 19th and early 20th centuries, Echinacea tinctures were very common in the United States. Publications report healing successes in diphtheria, syphilis, typhoid, cerebrospinal meningitis, chronic laryngitis and herpes (Webster, H.T. 1898).

In the older literature (Lloyd, J.U., 1904) a therapeutic effect with an Echinacea angustifolia preparation for cancer was reported. Prof. King in Cincinatti was able to use the preparation "Meyer's Blood Purifier" as the only means to improve the clinical situation of a woman with cancer for a long time. At the beginning of this century Echinacea preparations were also introduced in Europe.

The name of the Taraxacum belonging to the Compositae (family: daisy family / Cichoriaceae) is borrowed from Arabic-Persian (tharakhchakon = a daisy family). A derivation of the Greek terms ταpαξις (grinning stomach; eye inflammation) and ακεισθ ι (healing) seems conceivable. The name "taraxacum" was adopted in the Middle Ages from the writings of the Arab doctors Ibn Sina (Avicenna) and Serapion to avoid the name "Dens leonis' (dandelion), which has been known since the 13th century and recalls the toothed form of the Leaves.

Herbal book authors include the indications fever, cough, Gastrointestinal complaints, diarrhea, spitting blood and eye infections, taraxacum was also used as a diuretic and in wound care.

Römpp Chemielexikon, 9th edition, p. 2544 (1990) shows that dandelion extract has a stimulating effect on bile and kidney function, is therefore often part of blood purification teas and is consumed as a salad from freshly collected herbs. The plant contains sesquiterpene bitter substances (taraxin), triterpenes and taraxasterin, taraxasterol, taraxol, pectins, choline and inulin, especially in the roots, especially in the roots and leaves used officially.

For example, the diuretic activity of a Taraxacum mother tincture in white mice is known from various sources. Dandelion crude extracts were also examined for diuretic activity in mice, with a statistically significant natri and caliuretic activity in mice.

Herba Taraxaci's fluid extract can result in more than 30% weight loss compared to baseline in mice and rats after the end of treatment.

An increase in the bile flow after intraduodenal administration of the aqueous extract to rats has also been known for a long time. Aqueous extracts have no choleretic effect. Furthermore, it is known that Taraxacum officinale in a study on SCALD mice with suppressed immune status showed stimulating effects on cell-mediated immunity, the humoral and cellular immune system.

From older textbooks of biological remedies, compilations of clinical fields of application of Taraxacum officinale are known, which can be summarized under liver and gall ailments, cholelithiasis and jaundice, diabetes mellitus, blood cleansing agents, gastrointestinal disorders, nephro- and cystopathies, hemorrhoids and enuresis. There are also hepatocurative effects, - 4 -

namely the lowering of elevated serum bilirubin values, the normalization of pathologically changed bile pigment values in urine, the decrease in inflammatory liver swelling and the normalization of the rate of sedation.

The name "Plantago" is derived from It. "Planta", which means both "plant / seedling" and "sole of the foot" (especially the leaves of the plantain / Plantago major have a certain similarity to the sole of the foot). "Lanceolata" goes back to Latin "lancea": "lance", "spear" and refers to the narrow, pointed shape of the leaves of the plantain. The German name

"Plantain" refers to the location of the plant; it can be traced back to Gothic and Old High German ('hh [h] i': king) and originally means something like "master of the way".

Various types of Plantago were widely used as medicinal plants in the ancient world, and were prescribed by the Greek and Roman doctors against a variety of diseases for internal and external use. Theophrast (371-287) mentions the plant for the first time as "αpvoyλrüσσv" ("sheep's tongue", because of its leaf shape; Hist. Plant. VII 8, 3, etc.); It is described in detail in Dioskurides (1st century AD), which also mentions many of the later indications and lists a number of recipes that have been passed on by subsequent authors (De material medica II, 152). Pliny in particular. Ä. lists a large number of possible uses of Plantago (Nat. hist. esp. XXVI passim and XXV passim, botanical description XXV, 80); especially the astringent and cleansing effects of the leaves were highly appreciated.

The plant also plays an important role in medieval literature. In general, their hemostyptic, blood cleansing, antispasmodic and expectorant (and thus expectoration-promoting), antifebrile and wound healing effects are emphasized. - 5 -

The object of the present invention is to provide new drugs and thus new therapeutic options by using Echinacea pallida (EP) - and Echinacea angustifolia (EA) -, dandelions (Taraxacum, TA) - and ribwort (Plantago, PL) extracts.

Accordingly, a first embodiment of the present invention consists in the use of EP, EA, TA and PL extracts, in particular dry extracts for lowering the serum values of cholesterol, triglycerides, blood glucose, creatinine and / or bilirubin, GOT, GPT, GGT cellular immune stimulation, for the therapy of leukocytopenia, granulocytopenia, lymphocytopenia, thrombocytopenia, erythrocytopenia and for the treatment of radiation, infection and chemical-related damage to organs and tissues of the intestine, in particular the O-MALT system of the small intestine. of the lungs, bronchi and nasopharynx, bone marrow, thymus, spleen, lymph nodes, liver, pancreas and kidneys.

EP, EA, TA and PL experimentally increase liver parenchymal protein biosynthesis after oral administration. The pronounced activation of the liver metabolism also explains the clear clinical influence on the increased activities of liver-specific enzymes such as GOT, GPT, Gamma-GT, GLDH and LDH as a result of infectious hepatitis. EP, EA, TA and PL thus show curative effects on infectious liver cell damage.

Oral application of EP, EA, TA and PL experimentally induces stimulation of the hematopoiesis of all cell elements in the bone marrow, the lymphatic tissue in the Peyer's plaques, the mesenteric and cervical lymph nodes in the spleen and the intestinal-associated immune system (GALT = well associated lymphoid tissue) Thymus.

The stimulation of the normal activity of the lymphopoietic cell system, especially that of the T-lymphocytes (hyperplasia), documents the central event of the paramunization by Echinacea aar. This activated state will also influenced by the stimulation of liver parenchymal protein biosynthesis.

In the case of viral infection and carcinogenesis, the type and intensity of the initial immune response (paramunity) depends largely on the functional state of the T-

Regions in the lymphatic tissue in animals as well as in humans.

The oral application of EP, EA, TA and PL not only leads to a non-pathogen and non-antigen-specific protection (paramunity) against various infectious agents, but also increases the already developed - often reduced

- Induction of lymphatic activity due to infection. The therapy of herpes diseases with EP, EA, TA and PL in sufficient doses leads to an additional activation of the - often reduced - cell-mediated immune response with the clinical effects: significant suppression of the dissemination, rapid mitigation of the lesion with regard to redness, swelling and pain intensity.

As a result of the EP, EA, TA and PL application, a state of increased defense against infection (paramunity) is induced, which decreases again after the intake has been interrupted. The formation of a paramunity leaves no specific memory reaction (difference to immunity), which is why, for example, recurrent herpes simplex infections must be treated at intervals. The frequency of recurrence / year is often significantly reduced or even prevented by interval therapy.

Since EP, EA, TA and PL also stimulate granulocyte and macrophage phagocytosis, the antibacterial effect can also be justified. Based on experimental and clinical reports and examinations, EP, EA, TA and PL are clinically effective in bacterial and viral-induced diseases, such as: angina, bronchitis, laryngitis, otitis, sinusitis, lymphadenitis, eyelid margin infection,

Herpes labiaiis, genital herpes, herpes zoster, pharyngitis, influenza, ankylosing spondylitis. EP, EA, TA and PL are also helpful in the pre- and postoperative therapeutic phase of carcinomas.

EP, EA, TA and PL show no signs of undesirable effects, neither in the experimental studies carried out nor in clinical studies.

EP, EA, TA and PL extracts are administered orally, preferably in high doses (= high-dose phytopharmaceutical therapy) and, due to their variety of materials, obviously have a multigenic effect under immunological aspects. The multiantigenic effect of the extractive substances (synergy effect of the individual ingredients and active ingredients, multiantigenicity) ultimately induces non-specific immune stimulation (paramunization, immunomodulation, immunotherapy). EP, EA, TA and PL extracts act as paramunity inducers antiviral, antibacterial and antitumoral (anticarcinogenic).

Medication with immunoregulatory substances are substances that nonspecifically intervene in immune processes and intervene. (Mayer, A. et al. 1979).

The so-called immunostimulants seem to have in common that they are surface-active and activate the lymphocytes and macrophages responsible for the formation of immunity, such as gram-positive bacteria or their components. Listeria monocytogenes preferentially stimulates the B lymphocytes, Corynbacterium parvum the macrophages and BCG the T lymphocytes (Hahn 1978).

Paraspecific inhibitory effects on non-pathogen and non-antigen-related infections have also become known for numerous vaccinations, for example smallpox vaccinations for the therapy of herpes simplex or BCG vaccination as additional therapy for tumors. Paraspecific effects are induced by: a: increase in phagocytosis b: activation of the lymphopoietic cell system c: formation of interferon d: stimulation of humoral factors.

The local administration of the vaccine, especially orally and nasally, is apparently better for parasites than parenteral vaccination.

The increase in the defense against infections, the stimulation of the mechanisms responsible for immunity, the induction of interferon and the parasite-specific effects of certain vaccinations have one thing in common: They generate a rapidly developing pathogen and antigen-unspecific, more or less resilient protection against a majority of Infections (= Paramunität, Mayer, A. et al., 1979).

The formation of a paramunity leads to an increase in phagocytosis activity, to a better recognition, uptake and mediation of antigens - especially in T-lymphocytes - and thus to a faster development of the killer cells, effector cells derived from the antigen-specified T cells. Memory cells, helper cells and repressor cells, which together with the B lymphocytes regulate the immune mechanism centrally.

In connection with these induction, stimulation of the lymphopoietic cell system - especially that of the T lymphocytes - not only leads to a faster and stronger reaction with specific antigens, but also to an increase in the function of already antigen-specified T and B lymphocytes, whereby the stimulation of the T-cell-like repressor cells has a favorable regulatory effect (Mayer, A. et al., 1979).

An infiltration of macrophages in the spleen, liver and lymph nodes and an increase in monocytes in the circulation run parallel to these processes. The increased

The responsiveness of the phagocytic and lymphopoietic cell system does not appear to be due to a lymphopoetic multiplication of the phagocytes or lymphocytes to be based, but to be the result of an increase in metabolism (Mayer, A., et al., 1979).

A paramunity can be acquired naturally and artificially, both systemically and locally via the mucous membranes of the respiratory, digestion and urogenital tract. The locally acquired paramunity is of particular importance (Mayer, A. et al., 1979).

Oral application of EP, EA, TA and PL experimentally induces stimulation of the hematopoiesis of all cell elements in the bone marrow, lymphoid tissue, Peyer's plaques, mesenteric and cervical lymph nodes in the spleen via the gut-associated immune system (GALT = well associated lymphoid tissue) and thymus.

Treatment with EP, EA, TA and PL leads to an increase in the number of mobile B-lymphocytes in the follicles as well as the T-lymphocytes in the PALS, as well as to an increase in the lymphocytes in the peripheral blood. The stimulation of the normal activity of the lymphopoietic cell system, in particular that of the T lymphocytes, documents the central event of the paramunization by EP, EA, TA and PL. The observation that EP, EA, TA and PL clearly shows that the stimulation is obviously not based solely on a numerical increase in lymphocytes, but that it is the result of an increase in metabolism (Mayer, A. et al., 1979) increase the metabolic activity of the hepatocytes, which among other things leads to increased protein biosynthesis.

Corresponding in-vitro and experimental investigations by other authors with Echinacea purpurea extracts and individual substances isolated therefrom supplement the functional basics of parameterization by EP, EA, TA and PL described so far.

In detail it was proven: - 10 -

a: Stimulation of the granulocytes and macrophage phagocytosis b: Increased release of effector substances from granulocytes and

Macrophages, for example interferon, interleukin 1 and tumor necrosis factor c: increase in properdin level d: antiviral effect against influenza virus, genital herpes virus and

Viscular stomatitis virus.

In addition to activating the lymphopoietic cell system, EP, EA, TA and PL are primarily capable of the function and performance of granulocytes and macrophages - important immune-competent cells of the non-specific

Defense system - to stimulate.

In the patient studies with Echinacea purpurea, immunological effects were demonstrated which also demonstrate paramunization in humans: a: increase in granulocyte phagocytosis activity b: increase in lymphocyte activity in the NK cell test c: induction of an increase in the number of leukocytes d: Increase in cell-mediated immunity

A remarkable result of a patient study regarding the test for influencing the phagocytosis activity by a preparation from Echinacea purpurea is that according to p.o. Application a significantly higher stimulation rate than parenteral administration was measured. This paramunity acquired locally via the mucous membranes of the digestion tract is of particular importance (Mayer, A. et al. 1979), which is also particularly impressively confirmed by EP, EA, TA and PL through the effective therapy for bacterial and virus-related diseases .

Antitumor activity

A paramunity - the developing "immediate defense of an organism" can be acquired in a natural as well as an artificial way (Mayer, A. et al., - 1 1 -

1979). The protective effect of a naturally acquired paramunity against various infections also includes a protective function against carcinogenesis.

By using immunostimulants, neoplasts can be directly inhibited "by artificial means" by stimulating macrophages or T-killer cells (Wagner, H., 1,983).

Favorable survival prognosis for carcinomas due to a naturally acquired paramunity

In Vollmer, E. et al., Reaction Patterns of Lymph Nodes in the Development and Spread of Cancer, in Current Topics in Pathology, Berlin-Heidelberg, Vol. 84/2 (1991), the importance of the current immune status for the tumorigenesis is shown.

The effects of carcinogenic and transplantable tumor cells on the immune system of the rat were investigated in experimental studies. Obviously, an immune response occurs immediately in response to the initial carcinogen application: increase in T helper cells and later also in B and plasma cells, and a decreasing tendency for T suppressor cells.

In the further stage, attempts were made to determine the influence of tumor-associated factors and their prognostic values.

Paracortical hyperplasia is induced as early as 7 days after the injection of tumor cells. Reactions of the germ centers were observed in later stages of tumor growth, sometimes only after metastasis had broken out. On the 21st day, a clearly recognizable sinus histiocytosis developed, which decreased slightly as a result of advanced lymphogenic metastasis. Under the influence of an experimentally induced tumor, the histomorphology of the lymph node changes significantly chronologically even before - 12 -

Training of metastasis.

In the retrospective study of 65 patients, the changes in the lymph nodes due to colorectal cancer were histologically examined and their correlation with the survival time after the operation was documented. The average survival in group I (32 patients) was 16 months, in group II (33 patients) 59.7 months. Lymphatic hyperplasia was more common in group II (p <0.01), whereas a decrease in lymphocytes was more common in group I. The so-called "colorful hyperplasia" of the pulp was found even more frequently in group II than in group I (p <0.01). The mean relative volume of the diffuse paracortical areas was significantly larger in group III than in group I.

If only the preparations with the highest individual value per patient were compared with each other, the T cell areas and the undamaged pulp (paracortical zone and follicular cortex zone) of group II are significantly larger than those in group I (p <0.05) . It was striking that the size of the B cell areas had no correlation with the carcinogenesis of the colon carcinoma.

The results of the histological changes in the T cell areas in the lymph nodes during the phase up to metastasis allow a description of the status of the immune status and prognoses. The progression as well as the spontaneous regression of the tumor is not only influenced by the tumor but also by the type and intensity of the initial immune response (paramunity).

This answer is largely determined by the functional state of the T-lymphocyte-dependent paracortical zone in the lymph nodes in both animals and humans.

A herpes simplex virus (HSV) infection triggers a variety of humoral and cellular immune responses (paramunity). These host-specific answers - 13 -

induce a protective effect against dissemination during the first infection phase and shape the further course during the latent phase.

If the immune system is disturbed or damaged, the latency can often not be maintained. The result is reactivation of the virus, which can extend to extensive disseminations.

The antibodies formed by an initial infection with HSV 1 and 2 cannot provide complete protection against immunity in subsequent reinfections with the same or with the other virus type. However, the antibodies can reduce the severity of subsequent infections and shorten their duration.

Macrophages play a significant part in the defense against HSV infections. They are not only directly involved in the response of the T and B lymphocytes, but also. also crucial in controlling viral development. This includes phagocytosis of virions, the inhibition of viral replication by destroying virus-infected cells, and the induction of interferon production. This slows down or prevents the virus from spreading to non-infected cells.

The cellular immune response to a herpes infection is crucial for the recovery process

- the initial infection and

- the following relapse.

Patients with suppressed cellular immunity, for example as a result of malignant diseases, severe infections caused by AIDS, often develop severe herpetic mucosal infections or disseminated herpes infections. T-lymphocytes primarily exercise control functions in the herpes infection. Therefore, patients with suppressed cellular immunity with reduced or dysfunctional T cells are particularly susceptible to severe forms (Graham, Snell 1983). An example of this is infection with HIV (Human - 14 -

immunodeficiency virus), whereby the immunological primary deficit is characterized by the virus-induced damage to the helper T / inducer T lymphocytes (Clumek et al. 1984).

Studies with herpes labialis patients also show the activation of the virus-specific T cell subpopulations during the development of the relapse (Tsutsumi et al. 1986).

The expression of the cellular immune response is also important in patients with genital herpes (Corey et al. 1979). The importance of the protective function of thymic lymphocytes against HSV infections has been proven in numerous studies (Kapoor, et al. 1982, Nagafuchi et al. 1979).

Other immunosuppressive measures such as X-ray exposure, treatment with cyclophosphamide and an antithymocyte serum lead to a similarly clear susceptibility to progressive HSV infections (Oakes 1975, Rager-Zisman, Allison 1976).

If newborn thymectomized mice are infected with HSV, an immediate injection with immunized T cells can suppress the clinical picture (Kapoor et al. 1982).

As with carcinogenesis, the progression of HSV infection is decisively influenced by the type and intensity of the initial immune response (paramunity) by the lymphatic system.

Since the treatment with EP, EA, TA and PL "artificially" induces hyperplasia of the T regions with lymphoid tissue, this is also the reason why these substances, when dosed appropriately, spontaneously have a clinical curative effect on herpes simplex virus - Show illnesses. EP,

EA, TA and PL are obviously critical in controlling viral development by activating the macrophages and the - 15 -

lymphopoietic cell system - especially that of T-lymphocytes. EP, EA, TA and PL thus also stimulate virus-related, suppressed, cellular immunity.

Cellular immune responses are also directed against living cells or microorganisms. As a result of the specific antigen-antibody reaction (AAR), non-specific products are released, which lead to bacteriolysis and virolysis.

Immunity to bacteria is dominated not by specific and non-specific defense factors, but by the performance of antigen-unspecific phagocytic cells. These destroy the invaded microorganisms or prevent them from spreading. The clear curative effect of EP, EA, TA and PL on lid margin infections and sinusitis is obviously shaped by stimulation of the granulocyte and macrophage phagocytosis.

Preferred embodiments can be found in the dependent claims. According to the invention, in vivo studies on rats with a dry extract in dergal preparation as granules from the dried plant Echinacea pallida (EP), Echinacea angustifolia (EA), dandelion (Taraxacum TA) and ribwort (Plantago PL) were able to define defined parameters of the circulation - and immune system as well as defined functions of the liver, pancreas and kidneys. The test substances used EP, EA, TA and PL, which were used in an amount of 100 mg / KGW, induced:

an increase in the cell numbers of erythrocytes, thrombocytes, segmented granulocytes and lymphocytes, T, B, helper, suppressor and NK cells as an expression of cellular immune stimulation, with the dominant specific increase in B lymphocytes in particular (paramunization); - 16 -

a decrease in the levels of creatinine, bilirubin, urea, cholesterol, triglycerides, glucose, GPT and GOT.

The following are considered to be therapeutically desirable:

the lowering of cholesterol and triglyceride values in the sense of a positive influence on pathological fat metabolism disorders and thus a reduction of atherogenic risk factors;

- The general increase in defined immunocompetent cells as a possibility of non-specific treatment of inflammatory processes of different causal pathogenesis (paramunization);

the dominant specific increase in the cell numbers of the B lymphocytes as an adjuvant for the therapy of toxically triggered B cell suppression;

the decrease in bilirubin and the liver cell-specific activity value of GOT and GPT in terms of a hepatocurative effect;

- the decrease in the glucose level in the serum as a functional equivalent for a hypoglycemic effect;

the decrease in serum creatinine and urea as a sign of

Improvement of the renal function and detoxification of the ammonia produced in the protein metabolism and in connection with it

Reaction cycle an increased mitochondrial performance of the hepatocytes;

the increase in the number of erythrocytes, the hemoglobin content and the hematocrit value as an expression of an improved oxygen supply to the cell metabolism, no signs of undesirable effects.

The registered changes of defined hematological and clinical-chemical - 17 -

Analysis values are to be considered under two aspects: On the one hand, the results according to the invention of the parameters used speak for the curative and protective effects of the EP, EA, TA and PL extracts used described in the literature, and on the other hand for new - as yet unknown - biological effects that can be used from a therapeutic point of view for disorders of the carbohydrate metabolism, liver and kidney function as well as deficits of the cellular immune status (paramunization).

The object of the present invention is in particular to provide new use forms for Echinacea pallida and Echinacea angustifolia. The above object is achieved according to the invention by the use of Echinacea pallida and Echinacea angustifolia extracts for cellular immune stimulation for induction of an increased non-specific immune defense (paramunization), for adjuvant therapy for inflammation, for improving the oxygen supply to the cell metabolism, for improving the flow properties of the Blood, to improve renal function and to protect the liver and heal. According to the invention, the echinacea extract was examined in the context of an in vivo study in rats.

The oral application of Echinacea pallida (EP), Echinacea angustifolia (EA) experimentally induces stimulation of the hematopoiesis of all cell elements in the bone marrow, the lymphatic tissue in the Peyer's plaques, mesenteric and cervical lymph nodes via the intestinal associated immune system (GALT = well associated lymphoid tissue) in spleen and thymus.

Histologically, no changes in the structural elements characteristic of bone marrow, thymus, spleen, and mesenteric and cervical lymph nodes are observed when the clinically healthy lymphatic system is stimulated. In addition, the quality of the lymphoid cell elements of these organs does not change and no signs of increased mitotic activity are observed.

The micromorphological substrate of this orally induced stimulation speaks - 18 -

primarily for a quantitative improvement in the provision of physiological cell elements of the lymphatic group.

After application of an alkylating cytostatic that induces atrophy and lymphatic cell damage to the thymus, spleen, mesenteric and cervical lymph nodes, a partial accidental regeneration after treatment with Echinacea pallida (EP) and Echinacea angustifolia (EA) can be demonstrated. Micromorphologically, the corresponding organs show clear signs of a restoration of the organ-specific architecture and a clear repopulation of the reticular stroma with intact cells of the lymphatic system

Group.

This accidental regeneration of the lymphoreticular tissue shows no signs of an increased mitotic activity in the sense of a pathologically increased proliferation.

In the case of the lymph node, for example, histologically one can recognize a re-colonization of the reticular tissue with cells of the lymphatic group. In the paracortical zone there are densely packed, intact lymphatic cells, in the cortical zone there are loose, intact lymphocytes with a clear tendency towards subcapsular follicle formation. With the restoration of the characteristic microstructure of the lymphoreticular tissue in the lymph node, its function obviously starts again.

Recently, the various forms of reaction of the lymph node have gained practical importance: If stimulation of the T cells (paracortical zone) is observed in the drainage area of carcinomas (breast carcinoma, portiocarcinoma), the patient has a better prognosis than when the B cell is activated. Region or no lymph node response.

The successful defense against vital external causes of the disease by the body's immune system depends crucially on the strength and quality - 19 -

the host's immune response. An intact, cellular and humoral defense of the host organism can keep the development and spread of a tumor at bay. However, the most important source of immune deficiency today is cytostatic corticosteroid therapy in cancer patients. The results of extensive experimental studies ultimately confirm the excellent results that were observed clinically using high-dose therapy with Echinacea in the treatment of herpes simplex diseases or flu infections, as well as as an adjuvant in tumor therapy.

Another object of the present invention is to provide new application forms for dandelion extracts.

The above object is achieved according to the invention by the use of lion tooth extracts for cellular immune stimulation, for adjuvant therapy for inflammation, for improving the oxygen supply to the cell metabolism, for improving the flow properties of the blood, for improving renal function and for liver protection and healing function .

According to the invention, the dandelion extract was examined which, in comparison with a control group, induced:

Increase in the number of leukocytes, erythrocytes, platelets and

Hemoglobin content, the hematocrit value, the content values of potassium,

Calcium, protein and glucose, - a decrease in the levels of bilirubin, urea, cholesterol,

Triglyce den, creatinine, GLDH, GOT and GPT.

In the treatment group according to the invention, the cell numbers of the segmental nuclei increased in comparison with the control group. Granulocytes, T and B lymphocytes, helper and suppressor cells as well as NK cells clearly. - 20 -

The following are considered to be therapeutically desirable: the increase in the number of granulocytes, leukocytes and lymphocytes as well as the corresponding subsets as adjuvant for an anti-inflammatory effect (paramunization); - Lowering cholesterol and trigiyceride levels to improve

Fluidity of the blood; the marked reduction in creatinine and urea levels with the simultaneous increase in potassium as an improvement in renal function; the marked reduction in bilirubin and the enzymes GLDH, GOT and GPT as markers for a clear hepatoprotective and curative

Effect; the significant increase in the number of erythrocytes, the hemoglobin content and the hematocrit value as an expression of an improved oxygen supply to the cell metabolism.

It can be concluded from the results that the data of defined hematological, immunological and clinical-chemical parameters also in terms of the effects described in the literature, namely: aquaretic and diuretic properties - increase in bile flow, immunostimulatory and antitumor effects curative effects in hepatopathies

can be interpreted.

In this context, the found signs of a clear leukocyte-stimulating effect, which is characterized by an increase in the number of cells in the granulocytes, leukocytes and certain subsets (paramunization), are particularly noteworthy, since they are supported by various reports on taraxacum-specific effects.

According to the invention, the detection of a morphofunctional effect on the - 21 -

Metabolism of the liver and kidneys, as well as on the circulatory and immune systems.

For this purpose, male Wistar rats were divided into two groups and treated with dandelion extracts once a day for 7 days intragastric. Subsequently, blood was taken retroorbitally from the animals and then analyzed in vitro fully automatically and hematologically quantitative: leukocytes, erythrocytes, hemoglobin, hematocrit, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), mean hemoglobin concentration of the erythrocytes MCH.

In addition, leucocyte differentiation was carried out by flow cytometry after specific monoclonal incubation using fluorescence-activated cell sorting.

The clinical parameters such as bilirubin, creatinine, urea, GLDH, GOT, GPT, AP, glucose, cholesterol, triglycerides, calcium, sodium, potassium, chloride and total protein were recorded selectively, photometrically or with the aid of ion-selective electrodes.

The in vivo investigation showed that the standardized taraxacum extract (TDS) had a positive effect on the physiological metabolic relationships of the liver, kidneys and bone marrow.

It can be concluded from the results that the data of defined hematological immunological and clinical-chemical parameters obtained according to the invention can also be interpreted in the sense of the pharmacological effects described in the prior art, such as aquaretic, diuretic, bile flow stimulating, immunostimulating, curative and hepatocurative effects.

It could also be deduced from the data presented and the data available from the literature that dandelion extracts too - 22 -

Show protective effects against chemically-toxic noxae as well as against bacterial or viral infections and possess curative properties in the event of intoxication by chemically defined substances or in the case of hepatic clinical pictures.

In the present experimental study, dandelion extracts showed no undesirable effects at the tested dosage of 100 mg / kg body weight and the parameters used for the evaluation.

The fresh plant, in particular pressed juice, in dried form, in particular powder or infusion, is suitable as an application form, in particular as a tincture

Drops, granules, in particular capsule, and as tablets, in particular dragee or lozenge. For the purposes of the present invention, methanol is particularly preferably used as an extracting agent for the plant.

Another object of the present invention is to provide new uses for ribwort extracts.

The above-mentioned object is achieved according to the invention by the use of ribwort extracts for cellular immune stimulation, for induction of an increased non-specific immune defense (paramunization) and an increased function of the mucus-producing goblet cells in the epithelium of the small intestine and the bronchi in the lungs, furthermore the PL extracts, used for adjuvant therapy for inflammation, to improve the flow properties of the blood, to improve renal function and to protect the liver and healing organs.

According to the invention, the plantain extract was examined in the context of the in vivo study on rats.

Histological examination of mesenteric lymph nodes including the

Pancreatic lymph nodes, Peyer's plaques in the small intestine, spleen, thymus, and goblet cells of the small intestine and bronchi in the lungs - 23 -

Findings differing from the corresponding organs of the control animals from group I.

Under the influence of the test substance PL, micromorphologically demonstrable hyperplasia of the lympho-reticular tissue occurs in the secondary lymphatic organs mentioned (lymph nodes, subepithelial accumulations of lymphatic tissue, spleen and thymus), the T-lymphocyte areas appearing more stimulated than the B-lymphocyte areas . The hyperplasia of the paracortical zones impress in the lymph nodes and the Peyer's plaques, and the hyperplasia of the marginal zones in the spleen. The microarchitecture of the thymus is unchanged, but the density of lymphatic cells in the cortical zones is increased.

If one assumes that active substances which have an effect on the immune function and thereby significantly change the morphology of the T and B lymphocyte areas in the aforementioned lymphatic organs - both in terms of regression and stimulation - can be obtained from the present histological It has been found, in particular in the lymph nodes and spleen, that the conclusion is drawn that the oral administration of the test substance Plantago leads to considerable stimulation, in particular in the paracortical T-lymphocyte areas.

The signs of an increased formation of lymphocytes in the cortex of the thymus and the results of the hematological examination of the peripheral blood match this. In contrast, the bone marrow (in which the lymphocyte stem cells are located) of the animals from group II showed no morpho-functional differences in comparison with the bone marrow of the control animals.

According to this, oral treatment with PL primarily leads to an increased non-specific immune defense (Paramunität: Mayer et al. 1979), as it were ascending from the application site via Peyer's plaques and the subepithelial accumulations of lymphoid tissue into the lymph nodes of the abdominal cavity organs and ultimately the spleen. - 24 -

The increased secretion of T-lymphocytes as well as the other lymphocyte subsets could be measured in the present in vivo study after specific monoclonal incubation by means of fluorescence-activated cell sorting in the blood:

an increase in the number of cells of erythrocytes, thrombocytes, leukocytes, segmented granulocytes as well as of lymphocytes, T, B, helper, suppressor and NK cells as an expression of cellular immune stimulation; It should be particularly emphasized that there are no changes in the physiological relationships of these tested immunocompetent cell types.

The signs of an increased function of the goblet cells in the small intestine as well as the indicated increase in the proliferation of the glandular epithelium in all animals of group II (PL) can also be attributed to a local effect of the test substance.

The changes found in peripheral blood, characterized by a decrease in the content of creatinine, bilirubin, urea, GLDH, GOT, GPT, AP, cholesterol, triglycerides and glucose, are included in the conclusions drawn so far, since they reflect the metabolic aspect Morphofunctional changes in the organ systems described above can be assigned, for example lowering the transaminase and cholesterol of the increased synthesis activity of the liver cells.

The light microscopic examination of the liver in group II (PL) showed that the hepatocytes functioned largely in the same way in all animals in the form of large liver cells with large, bright cell nuclei (slight functional nuclear swelling). In comparison to the controls, only a low level of glycogen was found in the hepatocytes. This micromorphological

Group II liver substrate can be interpreted in terms of improved liver function. It would be conceivable to have this effect of Plantago in mind - 25 -

use a liver protection therapeutically.

All other organs, which were examined histologically according to the experimental plan, showed no differences in the comparison of the animals of the two groups.

Embodiment I. ^¬

Animals and ^~ ierhaltung Male Wistar rats were g with an average body weight of 321 under conventional conditions at a room temperature of 21 +/- 1 ° C, a relative humidity of about 60% and a 12 hour day held / night rhythm. Before the start of the experiment, they were subject to an acclimatization period of 12 days.

The diet was carried out with the pelleted standard diet Altromin C1000, Misch. No. 100 (Altrogge company, location); the animals received tap water ad libidum as drinking water.

PrDfsubsJanz

Drageekern granules with dry extract from dried roots of Echinacea pallida EP (Ch. No. 1134), extracting agent methanol 30 vol.%, Ch. No. 113934, herb of Taraxacum officinale (TD), extracting agent ethanol (60% v / v).

Application photo

1 mg of native dry extract (EP) was in 0.02 ml of aqua. least suspended.

The investigations were carried out with the standardized extracts in granulate form containing calcium carbonate and saccharide (auxiliary substances for the granulate form: calcium carbonate, monoxide, magnesium stearate, cellulose acetate phthalate, sodium carboxymethyl cellulose, talc, triacetin, arabic gum, camauba wax, sucrose, lactose and silicon dioxide, potato starch). 26

application

EP was administered intragastric to the non-sedated animals once a day for 7 days using a rigid button probe. The suspension was freshly prepared immediately before application and applied homogeneously.

Dose and treatment groups

Ten male Wistar rats were examined for the following

Treatment groups divided:

Group dose number of animals (mg / kg body weight)

I control group - 5 (comparison)

II EP (Invention) 100 5

Blood collection On the 7th day of treatment, 2 x 500 μl of blood was removed from the retroorbital venous plexus 2 hours after application, filled into vessels coated with sodium EDTA and mixed well.

To alytischa. Methods The aim of the investigations was to use a defined in-vivo model to simultaneously acquire specific markers that indicate the therapeutic effect as a synergistic effect of differently influenced physiological control circuits at an early stage.

The following were recorded in peripheral blood:

combined:

Erythrocytes, (Ery), leukocytes (Leu), platelets (Plt), hemoglobin

(HGB), hematocrit (HCT) - 27 -

Red cell indexes:

Mean cell volume (MCV), mean corpuscular hemoglobin (MCH), mean hemoglobin concentration of erythrocytes (MCHC) and erythrocyte distribution width (RDW)

flow cytometric:

Leukocyte differentiation: granulocytes, monocytes, lymphocytes, B and

T cells, helper and suppressor cells

- column chromatography:

Serotonin

combined:

GLDH, GPT, GOT, AP glucose,

Cholesterol, triglycerides,

Na, K, Cl, Ca,

Creatinine, urea, total protein.

With the aid of the fully automatic hematology analyzer Sysmex K-1000 the following can be determined: WBC, RBC, PLT as well as HGB and HCT, also MCV, MCH and MCHC. The main unit of this device essentially consists of a hydraulic (HS) and an electronic system (ES). The HS is used to aspirate, pipette, dilute, mix and lyse. The ES analyzes and converts the signals from the HS and transmits the results to the printer. With the help of microprocessors, the ES also monitors the test processes, the test station and carries out quality control.

The hematocrit value indicates the percentage volume of the erythrocytes in the blood. Hemoglobin, the chromoprotein contained in the erythrocytes, is an important criterion for the diagnosis of anemia in addition to the number of erythrocytes and the hematocrit value. The classification is based on the erythrocyte indices. - 28 -

Erythrocyte size and hemaglobin content are characterized by the erythrocyte volume (MCV = mean corpuscular volume), the hemoglobin content of the erythrocytes (MCH = mean corpuscular hemoglobin) and the mean corpuscular hemoglobin concentration (MCHC = mean corpuscular hemoglobin concentration). The red cell distribution width (RDW) is a measure of anisocytosis.

The parameters such as enzymes, glucose, lipids, electrolytes, creatinine, urea and protein are recorded with the aid of the Cobas Mira analyzer in a method-oriented, photometric or ion-selective manner.

The general well-being of the animals was checked during acclimatization before the start of the experiment and throughout the entire duration of the experiment. In addition, the body weight was determined daily.

All animals survived the intragastric application without impairments. The animals that were treated with the test substances showed no clinically adverse behavior until the end of the test.

E ιytrιr_oz.yie.α ,. eu ozytejD, Dirombozytejα

The potential of the test substance EP was indirectly determined by its stimulating effect on the number of leukocytes (WBS), erythrocytes (RBC) and thrombocytes (Plt).

The following was measured for the test substance EP: a significant increase in the number of leukocytes by 31.0%

Hemoglobin, J-iämatQkrit ΕrythrQzytenindices

The percentage increase in hemoglobin content as well as the hematocrit value in the treatment group (EP) collided with the corresponding increase in

Erythrocytes. Since the index MCV the quotient of hematocrit and

Number of erythrocytes, the index MCH the quotient of hemoglobin and - 29 -

If the number of erythrocytes and the index MCHC represents the quotient of hemoglobin and hematocrit value, it was understandable that these indices of the corresponding treatment groups were not clearly differentiated from those of the control group.

Leukocyte differentiation

The samples of groups I and II were analyzed in vitro by flow cytometry, the measurement of the cell size and the granularity making possible the discrimination of leukocytes, monocytes and granulocytes on the basis of the registration of corresponding scattering intensity. In addition, the strength of the immunopotentials of the test substances in group II (EP) with regard to their biological action was determined with the aspect of changing the cell number of the lymphocyte population. In vitro, T and B lymphocytes, helper and suppressor cells and NK cells were differentiated and quantified by flow cytometry using immunofluorescence.

In treatment group II, the cell counts of segmented granulocytes, T and B lymphocytes, helper and suppressor cells and NK cells were increased compared to the control group.

A significant increase was measured for the test substance EP by:

Leukocytes 30.99%

Lymphocytes 31, 16% - T cells 42.59%

B cells 26.04%

Helper cells 48.44%

Suppressor cells 39.17%

NK cells 25.86% - granulocytes 13.14%

Bilirubin, creatinine, urea, lipids, electrolytes and protein - 30 -

The following metabolic parameters were combined in a method-specific analysis:

Bilirubin, creatinine, urea, glutamate dehydrogenase (GLDH), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (AP), glucose, cholesterol, triglycerides, calcium, sodium, potassium, chloride and total protein.

A clear decrease was measured for the test substance EP:

- creatinine by -30.68%

Urea by -17.54%

GLDH by -18.32%

GPT by -18.05%

Cholesterol by -17.76% - triglycerides by -22.22%

Glucose by 7.18%

Example 2:

Testing of Echinacea pallida (EP) and Echinacea angustifolia (EA) after oral application for a regeneration potential with simultaneously induced alterations of the liver and lymphatic organs by cyclophosphamide.

The diagnostic-morphological examinations of the liver and lymphatic organs were developed in accordance with the "embodiment" model with the following additional test substances:

Drageekerngranulat with dry extract from dried roots of Echinacea angustifolia, Ch.Nr. 058937 (EA), cyclophosphamide (CyS): 1 mg CyS dissolved in 0.05 ml Auq. least 31

Group dose number of animals (mg / kg body weight)

I control group - 7 (comparison)

II EA (invention) 100 7

II EP (invention) 100 7

IV EA + CyS 100 + 10 4

V EP + CyS 100 + 10 4

The histological examinations were carried out after formalin fixation of the organ samples on paraffin sections (Medim Plast) with hematoxylin-eosin staining (H.E.) and additionally on the liver on frozen sections with fat staining (il-Rot-O).

Example 3:

Examination of the influence of "flu-like infections" and chronic forms of rhinopharyngeal bronchitis as well as sinusits caused by Echinacea pallida from the special aspect of frequency of recurrence (high-dose therapy)

The term "flu infection" refers to a viral infection of the respiratory tract which manifests itself in inflammation of the mucous membranes, which can be triggered by various viruses (e.g. influenza viruses, rhinoviruses, parainfluenza viruses, ECHO viruses, etc.). The "flu infection" is the most common human disease; the transmission takes place by droplet infection. The disease mainly occurs in the cold season, since hypothermia leads to reduced blood flow to the mucous membranes and the body's defenses are weakened. This explains the colloquial term "cold". Depending on the location of the infection, the "flu infection" manifests itself in the following clinical pictures: tracheobronchitis (trachea and central airways), rhinitis, tonsillitis, pharyngitis - 32 -

and laryngitis. The clinical picture of a "flu-like infection" is characterized to varying degrees by cough, runny nose, sore throat, fever, headache and body aches as well as by a general feeling of illness. The effectiveness of Echinacea aar Dragees was tested with a view to influencing the frequency and severity of recurrent, often chronic, forms of flu infections, rhinopharyngeal bronchitis and sinusitis. From February 1989 to October 1991, 19 patients with recurrent, often chronic flu infections, rhinopharyngeal bronchitis and sinusitis were enrolled in a general practice.

Criteria for the diagnosis of flu infections

Body aches, increased temperature, bronchitis, rhinitis, laryngitis, pharyngitis,

Weakness / lassitude, shivering / sweating, tearing / watering / burning eyes, nasal congestion / runny nose / secretion flow, sore throat / head pressure / hot head, coughing, redness in the throat. Rhinitis is a catarrhal or serous mucus inflammation, like a simple runny nose. Conjunctivitis also focuses on edema of the connective tissue with hyperemia, itching and lacrimation. In the area of the larynx, tracheal and bronchial mucosa there is a high degree of hyperemia with small bleeding as a result of stronger toxic vascular lesions, which give these mucous membranes a "flaming" flush. On days 2 to 3, epithelial and fibrin exudations (= fibrinous eschar or haemorrhagic damage) cause "flaky" scaly mucous membranes. Microscopically, edema with hyperemia and erythrocyte extravasation with lymphoplasmacellular infiltrations are typical. It can regenerate within 8 days, healing with restitutio ad integrum is the rule. Special diagnostic measures are not necessary. If the healing phase is not completed after 14 days, the clinical picture develops subacutely or chronically.

The viral-induced infections lead to mucosal lesions with damage to the cylindrical epithelium. The loss of these physiological barriers eases - 33 -

the bacterial invasion. Mostly different types of bacteria penetrate (= mixed flora), especially Streptococci, Staphylococcus aureus, pneumococci, Haemophilus influenzae, Eschericha coli and Klebsielles. The inflammation becomes more intense, there are dense trachea and bronchi, and even purulent bronchitis can occur.

Sinusitis

Headache / feeling of pressure, confused nasal breathing, reddening of the nasal mucosa,

Swelling of the nasal mucosa, pharynx in the throat, nasal and pharyngeal secretions, general fatigue, facial pain, chronic sinusitis, which can also be symptom-free (inspection of the throat, the height of the nose with speculum and rhinoscopy posteria or diaphanoscopy). As the cause of recurrent diseases of the respiratory tract, Beloradsky mentions deficiency in the immune system, which is largely not to be seen as immune deficiency, but rather as a temporary impairment of the immune system, caused by various factors from the patient's environment. The occurrence and severity of the clinical symptoms depend on the mass of the pathogen invasion and the respective immune system of the infected person.

Criteriaαiü zu & ätelicheJvled ika men.te

No other medication was permitted in the first 4 days of the disease apart from any necessary long-term medication (e.g. for heart failure, diabetes, etc.). Additional medication was recommended after the 4th day of illness if this did not interfere with the assessment of the experiment (e.g. no cough medicine with codeine). Permanent and secondary medication were documented by name when the data was collected.

Ablau dejL investigation

For the documentation, the patients were examined medically on the 1st, 4th and 10th day. The prescribed medication was given to the patient at the initial examination, in order to ensure that treatment began immediately and was the same for all patients. - 34 -

Medication: Echinacea pallida extract coated tablets were administered in the following standard dose: 3 x 3 coated tablets / day before meals.

Collection procedure: Each patient received instructions with instructions on how to record and evaluate their symptoms. During the first examination on the first day of illness, the value of the symptoms was determined jointly by the doctor and patient. It means: 0 = no complaints, 1 = minor complaints,

2 = slight complaints,

3 = moderate complaints,

4 = more severe complaints,

5 = severe complaints.

The "grading" of the symptoms of the disease improved over the course of the observation period, but also worsened. Information on the tolerability of the medication was requested.

Results

Therapy with 3 x Dragees Echinacea extract / day resulted in a clear clinical improvement in patients with recurrent, often chronic or subchronic infections with the predominant clinical pictures of rhinopharyngeal bronchitis. The severity and frequency of recurrences after interval treatment with echinacea compared to previous echinacea-free treatment courses in the same patients with subjective and clinical evaluation: a) a reduction in the sliding symptoms such as weakness, headache, limb, muscle and sore throat, Difficulty swallowing, earache, b) a marked reduction in susceptibility to influenza infections and thus a decrease in the frequency of certain recurrences / year, c) a reduction in the average duration of illness of Rhino-Pharyngo- - 35 -

Bronchitis from 9.5 to 5.25 days.

All treated patients rated the tolerance of Echinacea as "good to very good" and no side effects were observed. The therapeutic success was rated "good".

Example 4:

Studies of the effectiveness of Echinacea in herpes simplex virus diseases with a special focus on the frequency of recurrence (high-dose

Therapy)

Herpes infections are triggered by the herpes simplex virus (HSV), which occurs in the two main types HSV I and HSV II. The transmission takes place mostly in infancy or infancy through droplet infection or direct skin contact. In most cases, the primary infection is clinically normal and can only be detected by the presence of homologous antibodies. Despite the formation of antibodies, there is no complete elimination of the herpes simplex virus, which remains in the organism and leads to a non-productive latent infection phase.

A reactivation of the latent herpes simplex virus then leads to secondary and subsequent infections, i.e. to recurrent herpes. Various exogenous factors can be mentioned as the cause of the occurrence of recurrences: e.g. Infectious diseases, strong sun exposure, menstruation, mechanical trauma, food intolerance, psychological stress.

The characteristic feature of an infection with herpes viruses is that after the initial infection the viruses retreat along the nerve pathways that supply the entry area to the ganglia. They remain in this "hiding place" for a lifetime, in many cases without causing any symptoms of the disease. Only about ten percent of those infected have an initial infection - 36 -

Symptoms of illness; and only one percent of these have clinically serious symptoms.

In certain situations, however, the herpes viruses "sleeping" in the nerve nodes can be reactivated. Around eight to ten million Germans in Germany have a recurrence at more or less regular intervals - some even suffer from cold sores every month. The herpes viruses then migrate back to the area of skin into which they entered during the initial infections and cause the disease to break out again. Clinical observations indicate that a defect or change in the immune system is the possible cause of the relapse. For example, reactivity disorders of the immune cells were found in the lymphocyte transformation test, the macrophage inhibition inhibition test and the lymphocyte toxicity test. The reduced interferon production during HSV infection also indicates a reduced cellular immune competence.

Clinically, the herpes simplex diseases can be divided into two groups, which are characterized by their location. Herpes labiales diseases occur primarily on the lips, but also on the oral mucosa and the skin on the head and upper body, they are induced by HSV I. HSV II predominantly leads to genital herpes diseases (lower half of the body, especially the genital and gluteal regions). As prodronic signs of a disease, itching, burning and a feeling of tension may appear in the affected area. Subsequently, usually an erythema and mostly grouped, weeping vesicles develop. In addition, swelling and pain are very common. The lesions usually heal within about 10 days with scab formation.

The effectiveness of Echinacea coated tablets was examined in terms of influencing the frequency and severity of recurrent herpes simplex

Diseases carried out. - 37 -

In the practice for general medicine, 16 patients with recurrent herpes simplex diseases were included in the study.

In the protocol on which the study was based, in addition to the personal data of the patient, the recurrence of the skin symptoms and the localization of the skin symptoms were asked. Concomitant diseases and their treatment were also recorded. Before the start and at the end of therapy, the typical clinical signs of an HSV infection such as itching, pain, swelling, erythema and blistering were assessed. At the end of the study, the doctor and patient were asked about their assessment of the success of treatment, and the patient was also asked about the tolerance of Echinacea therapy. Side effects were to be described in detail with details of the type, intensity, time of occurrence and their duration, and treatment discontinuations were to be justified.

Since the investigation was carried out over a period of several months, statements were also made about the influence of Echinacea aar on the frequency of recurrence of herpes simplex disease.

Results

The treatment period until the herpes lesions healed averaged 5 days. In comparison to the usual average disease duration of 10 days, this must be seen as a clear treatment success of Echinacea therapy.

In two cases, the therapy even healed the lesions in 36 or 48 hours. In addition to the shortening of the duration of the illness, a marked reduction in the symptoms of itching, blistering, swelling and pain intensity was observed in all patients. The success of

Echinacea angustifolia / pallida extract therapy was rated "good or very good" by 16 patients. There were no side effects. - 38 -

With regard to influencing the frequency of recurrence / year, there was also a clear success of echinacea therapy. On average, the relapse rate dropped from 3.6 relapses / year before therapy to 1.35 relapses / year. 8 patients remained free of recurrence even after the successful echinacea therapy for longer than 6 months.

Overall, the success of Echinacea Therapy for Herpes Simplex Diseases was rated "good" on average by both the treating physicians and the patients. In general, there was a clear shortening of the course of the disease and less symptoms. In addition, the frequency of recurrence / year was significantly reduced.

Example 5:

Studies on the immune-active effect of Echinacea angustifolia / pallida (high-dose therapy)

First indications of a therapeutically utilizable effect of Echinacea angustifolia / pallida extract dragées on the cellular immune system with the help of the phenotyping of mononuclear cells could be verified.

1. If echinacea is administered simultaneously with radiation and chemotherapy in a dose of 3 x 3 coated tablets / day, the radiation or chemotherapy-related immunosuppressive potential can obviously be significantly reduced.

2. If Echinacea is applied following a radiation or therapeutic measure, it can be established that Echinacea with an application of 3 x 2 to 3 x 3 coated tablets over a period of 1 to 2 months reduces the therapy-related number of lymphocytes by approx. 30 to 50% and that of the granulocytes can increase by approx. 20 to 30%. - 39 -

3. If Echinacea is already applied in the pre- and postoperative phase as well as in the subsequent chemotherapeutic treatment phase, the results of the findings clearly show a clearer effect of curative immune stimulation than those that were determined in the case study in the Echinacea only in the postoperative, chemotherapeutic phase was administered.

Example 6:

Animals and animal husbandry

Male Wistar rats with an average body weight of 321 g were kept under conventional conditions at room temperature (21 +/- 1 ° C), a relative humidity of about 60% and a 12 hour day / night rhythm. Before the start of the experiment, they were subject to an acclimatization period of 12 days.

The diet was based on a standard pelleted Altromin C 1000 Misch diet. No. 100 (company Altrogge Lage).

The animals received tap water ad libidum as drinking water.

Test substances:

Drageekerngranulat with commercial dry extract from herb of Taraxacum officinale (TD) - extracting agent ethanol (60% v / v)

1 coated tablet with 300 mg contains dandelion extract 5.6-8.4 = 1) 150 mg application form: TD granules 1. 89 mg (= 1 mg native dry extract) were in 0.02 ml distilled water. suspended (TDS).

The investigations were carried out with the standardized extracts in granular form containing calcium carbonate and saccharide. (Excipients for the granulate form: calcium carbonate, iron oxide, magnesium stearate, cellulose acetate phthalate, - 40 -

Sodium carboxymethyl cellulose, talc, triacetin, arabic gum, carnauba wax, sucrose, lactose and silicon dioxide, potato starch)

Application TDS was administered intragastric to the non-sedated animals once a day for 7 days using a rigid button probe. The suspension was freshly prepared immediately before application and applied homogeneously.

Dose and treatment groups: 10 male Wistar rats were examined for the following

Treatment groups divided:

Group: Dose: Number of animals:

(mg / kg body weight) I control group (comparison) - 5

II TDS (Invention) 100 5

Blood

On the 7th day of treatment, 2 × 500 μl of blood were withdrawn from the retetroorbital venous plexus 2 hours after the application, filled into vessels coated with sodium EDTA and mixed well.

Analytical methods: (see embodiment 1)

All animals survived the intragastric application without impairments. The animals that were treated with the test substances showed no clinically adverse behavior until the end of the test. - 41 -

Erythrocytes, leukocytes, platelets

The potential of the test substance TDS was indirectly determined by its stimulating effect on the number of leukocytes (WBS), erythrocytes (RBC) and thrombocytes (PIt).

The following was measured for the test substance TDS: a significant increase in the number of leukocytes by 46.5% (corresponding values in the control group = 100%) - an increase in the number of erythrocytes by 6.9% and the

Platelet count by 6.8%

Hemoglobin, hematocrit, erythrocyte indices

The percentage increase in hemoglobin content as well as the hematocrit value in the treatment group (TDS) collided with the corresponding increase in erythrocytes.

Since the index MCV represented the quotient of hematocrit and erythrocyte number, the index MCH the quotient of hemoglobin and erythrocyte number and the index MCHC the quotient of hemoglobin and hematocrit value, it was understandable that these indices of the corresponding treatment groups were not clear in comparison with those of the control group were differentiated.

Leu o yieadiffer ^ nzisxung

The samples of groups I and II were analyzed in vitro by flow cytometry, the measurement of the cell size and the granularity making possible the discrimination of leukocytes, monocytes and granulocytes on the basis of the registration of corresponding scattering intensity.

In addition, the strength of the immune potential of the test substances in the - 42 -

Group II (TDS) was determined with regard to its biological effect under the aspect of changing the cell number of the lymphocyte population. In vitro, T and B lymphocytes, helper and suppressor cells and NK cells were differentiated and quantified by flow cytometry using immunofluorescence.

A significant increase was measured for the test substance TDS by:

Lymphocytes by 45.5%

T cells by 62.5% B cells by 24.7%

Helper cells by 49.7%

Suppressor cells by 71.0%

NK cells by 40.3% granulocytes by 53.0%

Bilirubin _^ creatinine, H_amsiαfiJ3lukose, _Lipid_e, electrolytes jndJΞiweiß The following metabolic parameters were combined and analyzed in a method-specific manner:

Bilirubin, creatinine, urea ,. Glutamate dehydrogenase (GLDH), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (AP), glucose, cholesterol, triglycerides, calcium, sodium, potassium, chloride and total protein. - 43 -

A clear decrease was measured for the test substances TDS:

Bilirubin by 67.2%

5.8% creatinine - 10.1% urea

GLDH by 10.7%

GOT by 14.7% GPT by 6.8% cholesterol by 6.3% - triglycerides by 26.8%

an increase measured by:

Potassium by 4.4% - Calcium by 3.0%

Protein by 4.6%

Glucose by 11.7%

Example 7:

Tier_e_unc XLerlιaItung

Male Wistar rats with an average body weight of 324 g were kept under conventional conditions at a room temperature of 21 +/- 1 ° C, a relative humidity of about 60% and a 12 hour day / night rhythm. Before the start of the experiment, they were subject to an acclimatization period of 12 days.

Test substance 44

Drageekerngranulat with standardized commercial dry extract from ribwort herb (3-6: 1); Extracting agent: purified water DAB 10, Ch.-Nr. 019144; Parent drug: Ribwort herb (Plantaginis lanceolatae herba) DAB 10; 1 coated tablet Plantago N with 445 mg contains 80 mg native plantain herb extract (3-6: 1; PL).

Application form

Ribwort herb N granules 5 mg (= 1 mg PL) native extract are in 0.02 ml

Aqua dest. suspended (PL), 0.5 ml PLS * 25 mg PL / 250 mg KGW.

The investigations were carried out with the standardized extracts in granulate form containing calcium carbonate and saccharide (auxiliaries for the granulate form: calcium carbonate, iron oxide, magnesium stearate, cellulose acetate phthalate, sodium carboxymethyl cellulose, talc, triacetin, arabic gum, carnauba wax, sucrose, lactose and silicon dioxide, potato starch.

application

PL was administered intragastric to the non-sedated animals once a day for 7 days using the rigid button probe. The suspension was freshly prepared immediately before application and applied homogeneously.

Dos Ls_and_Beiιan Lung sg tuppen

Ten male Wistar rats were examined for the following

Treatment groups divided:

Group dose number of animals (mg / kg body weight)

I control group - 5 (comparison)

II PL (invention) 100 5 - 45 -

Blood

On the 7th day of treatment, 2 hours after application, 2 × 500 μl of blood were withdrawn from the retroorbital venous plexus, filled into vessels coated with sodium EDTA and mixed well.

Analytical methods (see example 1)

Erythrocytes, leukocytes, thrombocytes The potential of the test substance PL was determined indirectly through its stimulating effect on the number of leukocytes (WBS), erythrocytes (RBC) and platelets (PIt).

The following was measured for the test substance PL: a clear increase in the number of leukocytes by 41.8% and an increase in the number of erythrocytes by 5.5%

HämogiQb.in, _Hämato_krJt, __ erythrocyte indices

The percentage increase in hemoglobin content as well as the hematocrit value in the treatment group (PL) collided with the corresponding increase in erythrocytes.

Since the index MCV represents the quotient from hematocrit and erythrocyte number, the index MCH the quotient from hemoglobin and erythrocyte number and the index MCHC the quotient from hemoglobin and hematocrit value, it was understandable that these indices of the corresponding treatment groups were not clear in comparison with those of the control group were differentiated.

Leukocytendifferenzieαing The samples of groups I and II were analyzed in vitro by flow cytometry, with the measurement of cell size and granularity based on the registration of corresponding scattering intensity, the discrimination of leukocytes and monocytes - 46 -

and granulocytes.

In addition, the strength of the immunopotentials of the test substances in group II (PL) with regard to their biological action was determined with the aspect of changing the cell number of the lymphocyte population. In vitro, T and B lymphocytes, helper and suppressor cells and NK cells were differentiated and quantified by flow cytometry using immunofluorescence.

In treatment group II, the

Cell numbers of segmented granulocytes, T and B lymphocytes, helpers and suppressor cells and NK cells increased.

A significant increase was measured for the test substance PL of: - leukocytes by 41.8%

Lymphocytes by 44.2%

T cells by 57.5%

B cells by 42.7%

Helper cells by 46.9% - suppressor cells by 53.3%.

NK cells by 15.6%

Granulocytes by 17.5%

B iü rjJn, _. Kr_eatinin Jiari ^^ The following metabolic parameters were combined and analyzed in a method-specific manner:

Bilirubin, creatinine, urea, glutamate dehydrogenase (GLDH), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (AP), glucose, cholesterol, triglycerides, calcium, sodium, potassium, chloride and total protein. -47-

A clear decrease was measured for the test substance PL:

Creatinine by 12.4%

Urea by 14.0%

GLDH by 11.8% - GOT by 10.5%

GPT by 23.7%

Cholesterol by 13.8%

Triglycerides by 31.8%

an increase measured by:

Sodium by 5.7%

Potassium by 17.1%

Claims

- 48 - PATENT CLAIMS

1. Use of Echinacea pallida (EP), Echinacea angustifolia (EA), dandelion (Taraxacum, TA) and / or ribwort (Plantago, PL) extracts, in particular dry extracts from the fresh or dried plant for the production of Medicines for the treatment or prevention (protection) of radiation (radio prevention, protection), infection (infection prophylaxis) and chemically-related organ and tissue damage (chemoprevention, protection, especially of the O-MALT system of the small intestine (inflammatory diseases, enteritis regionalis Crohn) of the lungs (inflammation, disease) of the bronchi and nasopharynx (rhinopharyngeal bronchitis, rhinitis, pharyngitis, sinusitis), bone marrow (bone marrow aplasia), thymus (dysfunction, apiasia or hypoplasia due to medication or radiation-related damage), the liver (atrophy, necrosis), hepatitis A, B, and C of the pancreas, insufficiency of the exocrine, secretory function of proteas s, esterases, carbohydrases and nucleases as well as the endocrine dysfunction of carbohydrate metabolism (Langerhans Islands) and the kidneys (insufficiency) as well as of general immunosuppressed conditions, for cellular immune stimulation, for the therapy of leukocytopenia, granulocytopenia, lymphocytopenia, erythrocytopenia, thrombocytopenia, thrombocytopenia, thrombocytopenia, thrombocytopenia, thrombocytopenia, thrombocytopenia, and thrombocytopenia, and thrombocytopenia, and thrombocytopenia, among other things ) and in immunoglobulin deficiency, also as a result of AIDS, tumors and diseases with suppressed immune systems.

2. Use according to claim 1, characterized in that the cellular immune stimulation (paramunization), in particular after immunosuppression by radiation or chemotherapy treatments, ie the increase in the number of cells of leukocytes, segmented granulocytes and lymphocytes, T, B, helper, Suppressor and NK cells, in particular of B lymphocytes in the terminal current pathway, have the effect that an increase in vital lymphocytes in the bark zone and the follicles in the Peyer's plaques (small intestine) can be seen, which is associated with a secretory induction of sIGA in the small intestine is connected that a - 49 -

An increase in all blood formation elements in the bone marrow can be ascertained that cellular stimulation of immunocompetent cells in the thymus, spleen and mesenteric lymph nodes is detectable and / or that the metabolic functions of the liver, pancreas and kidneys (reduction in the serum values of creatinine, uric acid, glucose, bilirubin, cholesterol and Triglycerides as well as GOT, GPT and GGT) are clearly activated.

3. Use of EA, EP, TA and PL extracts according to claim 1, high-dose phytopharmaceuticals, in particular in a dose for Echinacea 300-2700 mg / day ≥ 2-3 x 1 to 9 coated tablets of 100 mg native

Extract,

Dose for Taraxacum 600 - 5400 mg / day = 2-3 x 1 to 6 coated tablets of 300 mg native

Extract,

Dose for Plantago 300 - 3600 mg / day = 2-3 x 1 to 12 coated tablets with 100 mg native extract.

4. Use according to claim 1 or 2 for the treatment of disorders of carbohydrate metabolism and liver and kidney function, for the treatment of hypercholesterolemia, hypertriglyceridemia, prediabetic, in particular senile veriaufsformen for the treatment of infections in combination with chemically defined antidiabetic agents.

5. Use according to claim 1 or 2 as oral adjuvants of malignant tumor treatment, in particular the treatment of breast, portio, colon or prostate cancer, also in combination with cytostatics, in particular cyclophosphamide or radiation therapy, and the treatment of AIDS and diseases with suppressed immune system.

6. Use according to claim 1 to increase the tolerance of chemo-, cytostatic, radiological therapy, in particular in combination with chemically defined substances selected from cytostatic agents, such as cisplatin, cyclophosphamide, methotrexate, fluorouracil, bleomycin and / or clofibrate, ACE inhibitors, α- 2- - 50 -

Receptor antagonists, Ca antagonists and / or diuretics, as adjuvants for analgesia, in particular as a pharmacological component for positively influencing the interactions between the endocrine, nervous and immune systems.

7. Use according to claim 1 or 2 as an adjuvant in the treatment of bacterially and virally induced clinical pictures, in particular inflammatory diseases of the small intestine (Enteritis regionalis Crohn), the lungs, the pancreas and the kidneys, liver atrophy, hepatitis A, B and C, skin lesions (Ulcus cruris), as well as herpes simplex I and II and herpes zoster,

AIDS.

8. Use according to one or more of claims 1 to 6 as a fresh or dried plant, in particular pressed juice or in extracted form with the aid of aqueous, organic and / or supercritical solvents, in particular carbon dioxide; in dried form, in particular powder, dry extracts from the fresh plant or drug (dried plant, granules, in particular as a capsule and as a tablet and as a dragee or lozenge).

9. Use according to one or more of claims 1 to 7, characterized in that Echinacea, Taraxacum or Plantago extracts with a drug / extract ratio (DEV native) of 4-9: 1 are used.

10. Use according to one or more of claims 1 to 9, characterized in that the Echinacea pallida, Echinacea angustifolia, dandelion (Taraxacum) - and ribwort (Plantago) - extracts combined individually or with each other or in each case in combination with Cynara and / or mistletoe (viscum) extracts and / or with nettle (urtica) extracts, in particular dry extracts from the roots, leaves or herbs, furthermore with birch leaf (betula) extracts and with putamen ovi preparations on the basis of

Eggshell components, in particular the central pallisade and mammill zone, optionally in combination with chemically defined chemotherapeutic agents, - 51 -

Antibiotics, diuretics, cytostatics to inhibit bone demineralization and / or depression for malignant tumor treatment, in particular the treatment of primary and secondary bone tumors, breast, portio, colon or prostate cancer as well as tumor anemia and infectious anemia.

11. Orally administrable medicament containing Echinacea pallida, Echinacea angustifolia, dandelion (Taraxacum) - and ribwort (Plantago) - dry extracts, as in one or more of claims 1 to 10, defined in granular form containing calcium carbonate and saccharide.