Active ingredient: Extract from Cimicifuga rootstock

1
Active ingredient Extract from Cimicifuga
rootstock
Indication Climacteric disorders
2
Hormonal changes during climacteric period
Source F. Borrelli et al. / Life Sciences 73
(2003) 1215-1229
3
Hormonal changes during climacteric period
Climacteric
.
Premenopause Menopause Postmenopause
4
Black cohosh - a gentle and natural alternative
to hormone substitution
The end for the classical hormone therapy?
A study of the Womens Health Initiative (WHI)
with 16,609 women was abandoned prematurely due
to a bad benefit/risk proportion!
Source JAMA 2002, 288 (3) 321 - 333
5
The end for the classical hormone therapy?
The probands took in daily, for on average 5.2
years, a combination preparation of conjugated
estrogen (0.625 mg) and medroxyprogesterone-acetat
e (2.5 mg/d) compared to placebo - thromboembolis
ms 100 - cerebral apoplexy 41 - risk of
breast cancer 26 - myocardial infarcts
29 - hip fractures (osteoporosis) - 33 - colon
cancer - 37
Source JAMA 2002, 288 (3) 321 - 333
6
Botany
Cimicifuga racemosa (L.) Nuttal
Family Ranunculaceae (crowfoot
plants). Synonyms Black snake root, Bugbane,
Rattleroot, Squaw root Origin Eastern and
central part of North America, Canada, Europe,
moderate to arctic parts of Asia.
7
Botany
Cimicifuga racemosa (L.) Nuttal
Medicinal drug Black cohosh rootstock,
Cimicifugae rhizoma. After the fruits have
become ripe in autumn, the rhizome is
collected, dried and cut up. The fresh or
dried rootstock with attached roots is used for
production of the extract.
8
Brief profile - Black cohosh

• The enduring plant can reach a height of up to 2
  m.
• The upright stems have big, multiple-feathered
  leaves with deep-sawed small leaves.
• The small white blossoms build long narrow
  clusters.
• The originating fruits are ovoid capsules which
  contain numerous flat seeds.
• The rootstock which is used for extraction of the
  drug is dense and branched.

9
Ingredients

• triterpene glycosides (actein, cimicifugoside)
• isoflavonoids
• essential oil
• bitter substances
• resins
• several fatty acids

The drug basically contains triterpene glycosides
of the type cycloartenol, e.g. actein and
cimicifugoside.
10
Therapeutic principle Total extract
The estrogen-like ingredients attack in
mesolimbic and hypothalamic structures

• selective reduction of the LH-secretion
• no influence on the FSH- and prolactin level
• contains phyto-SERMs (selective estrogen
  receptor modulators)
• without undesired effects on uterus, mamma
• reduction of the osteoporosis and
  arteriosclerosis risk
• no undesired effects on the endometrium
• estrogen-like effect

11
Therapeutic principle

• LH-suppression (suppression of the hypothalamic
  LHRH pulse generator)
• binding to estrogen receptors (competitively to
  estradiol)
• stabilisation of neurovegetative symptoms
  (effect on the vasomotor centre, balance vagus -
  symphaticus)

12
Therapeutic principle
Hormonal circuit of regulation
at normal production of estradiol
in menopause
Source ÄP Gynakologie 2000
13
Therapeutic principle
Endocrine regulation
14
Fields of application
Traditional

• Ancient medicinal plant of the North American
  Indians
• use against snake bites
• in case of painful menstruation
• for easing of the birth process
• as fresh pressed juice with honey
• as good preparation for cough
• for tinnitus and particular diseases, socialised
  with certain depressions

15
Fields of application
In menopause
About 1940 introduction of Cimicifuga in the
therapy of premenstrual und climacteric
disorders.

• hot flushes and outbreaks of sweat
• tiredness and lack of motivation
• sleep disorders
• weight changes
• headache
• articular and muscular pain
• ventricular tachycardia
• sometimes urinary incontinence
• weakness of concentration

16
Fields of application
In menopause

• irritability
• anxiety
• depressive moods
• irregular menstruation
• decreasing libido
• dry skin and mucosa
• pains during the sexual intercourse
• falling out of hair, greasy hair

17
Clinical efficacy
Rational phytotherapy with Cimicifugae racemosae
rhizoma
Pre-clinic
In-vitro study precludes proliferative effect on
estrogen-sensitive mammary carcinoma
cells Bodinet C, Freudenstein J (2002)
Influence of Cimicifuga racemosa on the
proliferation of estrogen receptor-positive human
breast cancer cells. Breast Cancer Res Treat 76
(1) 1-10
18
Clinical efficacy
Rational phytotherapy with Cimicifugae racemosae
rhizoma
Pre-clinic
Extract from Cimicifuga does not show any
estrogen-like stimulation of tumour growth in the
animal model Freudenstein J, Dasenbrock C,
Nisslein T (2002) Lack of promotion of
estrogen-dependent mammary gland tumors in vivo
by an isopropanolic Cimicifuga racemosa extract.
Cancer Res. 62 (12) 3448-52
19
Clinical efficacy
Rational phytotherapy with Cimicifugae racemosae
rhizoma
Pre-clinic
Extract from Cimicifuga in case of
osteoporosis Nisslein T, Freudenstein J (2003)
Effects of an isopropanolic extract of Cimicifuga
racemosa on urinary crosslinks and other
parameters of bone quality ovariectomized rat
model of osteoporosis. J Bone Miner Metab 21 (6)
370-6
20
Clinical efficacy
Rational phytotherapy with Cimicifugae racemosae
rhizoma
Therapy studies
Placebo-controlled study Düker E et al. (1991)
Effects of extracts from cimicifuga racemosa on
gonadotropin release in menopausal women and
ovariectomized rats. Planta Med 57 420-424

• Extract from Cimicifuga does not influence the
  FSH- and prolactin level

21
Clinical efficacy
Rational phytotherapy with Cimicifugae racemosae
rhizoma
Therapy studies
Double-blind, randomised study Stoll W.
(1987) Phytopharmacon influences atrophic
vaginal epithelium double-blind study
Cimicifuga vs. estrogen preparation.
Therapeutikon 1 23-31

• Extract from Cimicifuga can absolutely be
  compared with estrogens

22
Clinical efficacy
Rational phytotherapy with Cimicifugae racemosae
rhizoma
Therapy studies
Three-armed double-blind study Wuttke W,
Seidlova-Wuttke D, Gorkow C (2003) The
Cimicifuga preparation BNO 1055 vs. conjugated
estrogens in a double-blind placebo-controlled
study effects on menopause symptoms and bone
markers. Maturitas 44 Suppl 1 67-77 Osmers R
(2004)Efficacy and tolerability of an
isopropanolic extract from the rootstock of the
Black cohosh. Abstract on the lecture.
Phytopharmaka und Phytotherapie 2004, Forschung
und Praxis, 26.-28. Februar 2004, Berlin

• Extract from Cimicifuga improves psychovegetative
  complaints clearly

23
Cefakliman mono - advantages at a glance

• Gentle and natural alternative to hormone
  replacement therapy
• Regulation of hormonal disharmonies
• Normalisation of psychosomaticand vegetative
  disorders in menopause

24
Basic information
Fields of application For improvement of
psychical and neurovegetative disorders caused
by the menopause. Composition Active
ingredient 1 capsule contains Cimicifuga
rootstock dry extract (4 1) 5 mg.
Excipients Lactose monohydrate, colloidal
anhydrous silica, microcrystalline cellulose,
povidone, gelatin, titanium dioxide (E 171),
erythrosine (E 127), indigotine (E 132), ferric
oxide red (E 172), ferric oxide black (E
172). Contra-indications If patients, suffering
from estrogen-dependent tumours, are/were in
medical care, Cefakliman mono must not be used
as it is not known if Cimicifuga rootstock
extracts support estrogen-dependent tumours or if
they do not have any influence. There has not
been sufficient research for the application of
this medicine during pregnancy and lactation.
Therefore it should not be used during this
period.
25
Basic information
Interactions with other medicaments None
known. Precautions for use and warnings During
the treatment liver function tests must be
followed up. The long-term usage of Cimicifuga
racemosa preparations can have rare side effects
on the liver. Therefore, if you notice fatigue,
anorexia, yellowness of the skin and eyes, pain
of stomach, nausea, vomiting or darkness of urine
during the use of Cefakliman mono you should
stop usage and tell your doctor. Dosage Unless
otherwise prescribed, adults take 1 capsule twice
daily. Kind and duration of application Cefaklima
n mono capsules are taken with some liquid (e.g.
water). The duration of the treatment is
generally not limited, but Cefakliman mono
should not be taken for more than 3 months
without medical advice.
26
Basic information
Side effects Occasionally gastric disorders. An
increase in weight is possible. Commercial
form Capsules 50 pcs.
27
Monograph
Black Cohosh root, Cimicifugae racemosae
rhizoma Official Monograph of the Bundesinstitut
für Arzneimittel und Medizinprodukte (BfArM)
(German Federal Institute for Drugs and Medical
Devices) Commission E (Phytotherapy), BAnz.-No.
228 dated March 02, 1989 Name of
Drug Cimicifugae racemosae rhizome, black cohosh
root. Composition of Drug Preparations of black
cohosh consist of the fresh or dried rhizome with
attached roots of Cimicifuga racemosa (L.) Nutt.
Fam. Ranunculaceae in effective dosage. The
drug contains triterpene glycosides. Uses Premens
trual discomfort, dysmenorrhea or climacteric
menopausal neurovegetative ailments. Contraindi
cations None known.
28
Monograph
Side Effects Occasionally, gastric
discomfort. Interactions with Other Drugs None
known. Dosage Unless otherwise prescribed Daily
dosage Extracts with alcohol 40 60 percent
(v/v) corresponding to 40 mg of drug. Mode of
Administration Galenical preparations for
internal use. Duration of Administration Not
longer than 6 months. Actions Estrogen-like
action Luteinizing hormone suppression Binding to
estrogen receptors