CIRCULAT in Chronic Ischemic Heart Disease - 20 Pat, Diabetic Foot and Gene Expression

CIRCULAT IN CIRCULAT IN CHRONIC ISCHEMIC CHRONIC ISCHEMIC

HEART DISEASEHEART DISEASE

Centro Médico Docente AdaptógenoWho are we ?

• Most widespread private medical network (Vzla);

• Application of a proprietary therapeutic solution

(Systemic Medicine);

• 150 orthodox medical doctors;

• 45 Medical Centers and Units (Vzla); and Puerto Rico (3);

• Overseen > 1 mill. patients (2002-10).

Puerto Rico

Venezuela

Genetic Modulator

• CIRCULAT as a Gene expression modulator

• CIRCULAT in Diabetic Foot Management

• CIRCULAT in Chronic Ischemic Heart Disease

CIRCULAT Background Studies

Pennsylvania State University, 2007

Faculty of Medicine

187 modulated genes

with Circulat

August, 2007

STUDY

Evaluation of the changes in the Evaluation of the changes in the genetic expression after genetic expression after

CIRCULATCIRCULAT

Objective: Objective: To reveal the underlying molecular mechanisms to the To reveal the underlying molecular mechanisms to the

biological activity of the Circulatbiological activity of the Circulat. .

Gene Expression

HIGHLIGHTSModulation of Genes Associated

with the origin of Diabetes

• IL6: inflammatory mediator, glucose regulator in pancreatic beta cells

• HMGA1: Counters insulin resistance• SLC19A2: Associated with Diabetes

pathogenesis• C4A: Associated with diabetes origin

HIGHLIGHTSModulation of Genes Associated

with the origin of Cardiopathy

• TRPM2: Atherosclerosis• ATP5F1: ATP Sinthesys • CYP3A4: Oxidative Phosphorilation• NMNAT2: Anaerobic Glycolysis

Modulation of 24 Pathological Genes• PGK1 Hemolytic anemia due to PGK deficiency Myoglobinuria/hemolysis due to PGK deficiency• MYO1A Deafness, autosomal dominant no nsyndromic sensorineural• PRKAR1A Adrenocortical tumor, somatic Carney complex, type 1 Myxoma, intracardiac Pigmented

adrenocortical disease, primary isolated Thyroid carcinoma, papillary• AHI1 Joubert syndrome-3• SYN2 Schizophrenia, susceptibility to C4A• UROD Porphyria cutanea tarda Porphyria, hepatoerythropoietic• WNK1 Pseudo-hypo-aldosteronism, type II• NR4A3 Chondrosarcoma, extraskeletal myxoid • RAB7 Charcot-Marie-Tooth disease, type 2B • IL6 Diabetes type 1 and 2 Osteopenia, osteoporosis, Kaposi sarcoma, susceptibility to • SAT Keratosis follicularis spinulosa decalvans• SOCS3 Dermatitis, atopic, 4 • PDE4D Stroke, susceptibility to, 1 • SLC19A2 Diabetes type 2 Thiamine-responsive megaloblastic anemia syndrome • RAB3GAP1 Warburg micro syndrome 1 • ENTH Schizophrenia, susceptibility to• CD55 Blood group Cromer • ALDOB Fructose intolerance • LHX4 Short stature, pituitary and cerebellar defects, and small sella turcica\ Amyotrophic lateral

sclerosis 8Spinal muscular atrophy• VAPB Spinal muscular atrophy, late-onset, Finkel type LPPLeukemia, acute myeloid Lipoma• HMGA1 Diabetes type 2Lipoma• FANCB Fanconi anemia, complementation group B Breast cancer, early onset• BRIP1 Fanconi anemia, complementation group J• C4A Diabetes type 1

CIRCULAT: Gene expression modulator

CIRCULAT in Diabetic Foot Management

• CIRCULAT has been used very successfully in the CMA Network for the treatment of circulatory disorders.

• CIRCULAT achievements in circulatory disorders was also replicated in the treatment of diabetic foot (and varicose ulcers). This warranted a clinical study.

• Thus, a retrospective study was carried out in 174 diabetic foot patients treated between 2004 – 2007.

Publication: 2008

Diabetic Foot Results with Circulat174 patients; 88.5% Efectivety

STUDY

Results Stable Angina Pectoris Estudio realizado en 83 pacientes

Mejoría significativa 85%

Male, 64 years: evolution ‘years’

After 6 month treatment

Clinical Outcomes of Diabetic Foot Management with Circulat(Example of Study’s photographic evidence)

Female, 61 years, evolution ‘months’

After 6 months treatment

Diabetic Foot

Male, 58 years, evolution 6 months

Diabetic Foot

After 4 months’ treatment

After 2 1/2 months of treatment

Male, 56 years, evolution “years”

Diabetic Foot

After 9 months of treatment

Female, 65 years, evolution 15 days

Diabetic Foot


Female, 59 years, evolution 7 months

Diabetic Foot

Female, 67 years, evolution 2 years. After 7 months of treatment

Diabetic Foot

Female, 61 years, evolution “months”


Diabetic Foot

After 2 months of treatmentFemale, 49 years, evolution 1 year

Diabetic Foot

After 9 months of treatmentMale, 44 years, evolution 1 month

Diabetic Foot


Male, 46 years, evolution 4 months.

Diabetic Foot

Male, 62 years. Evolution“years”


Diabetic Foot

Female, 47 years. Evolution “months”


Diabetic Foot

Female, 79 years: evolution 2 years

After 6 year treatment

Photographic Evidence Varicose Ulcer

Female, 42 years: evolution 14 months



Female, evolution 30 years




Male, evolution 1 years


After 2 month’s treatment


Before After

CMA Lecherías

H.C. 22728

Dra. Luz Méndez

Photographic Evidence Arterial Ulcer

Before After

CMA Sta Mónica

HC: 4097

Dra.. Gladys Vargas


Before After

CMA Lechería

H.C. 22.970

Dra.. Luz Méndez


Before After

CMA Lechería

H.C. 26629

Dra. Luz Méndez


Before After

CMA SabanaGrande

H.C: 57.394

Dra.: Runi Molina


Before After

CMA Sabana Grande

H.C. 30.195

Dra. Runi Molina


Before

After

CMA Barquisimeto

H.C. 28.212

Dr. Rolando Sequera


Before

After

CMA Lechería

H.C. 26.213

Dra. Magaly Tinoco


Before After

CMA Lechería

H.C. 18970

Dr. Nerio Villalobos


Before After

CMA Lechería

H.C. 19.121

Dra. Mª Osorio


Before After

CMA Lechería

H.C. 12.316

Dr. Wilfredo Sánchez


Before

After

CMA Sabana Grande

H.C. 57.943

Dra. Edith González


Before After

CIRCULAT Study in Chronic Ischemic

Heart Disease

Patrick J. Lynch, 2006

Background: Endothelial Damage

NORMAL ARTERY ATHEROSCLEROTIC PLAQUENARROWED ARTERY

ENDOTHELIUM

SMOOTH MUSCLE

SMOOTH MUSCLECELLS

MACROPHAGESTRANSFORMED

INTO FOAM CELLSLIPIDS, CALCIUM

CELLULAR DEBRIS

FIBROUS CAP.

ENDOTHELIUMDAMAGE

ENDOTHELIALDYSFUNCTION

MECHANICALSTREESS

HYPERTENSION

VASOCONSTRICTION

PERIPHERALVASCULAR RESISTANCE

Relevant Mortality Rates in Venezuela

Chronic Ischemic Heart

Disease GSPECT Assessment

(Independant Lab)

Treadmill

Imaging

Chronic Ischemic Heart

Disease GSPECT Assessment

(Independant Lab)

Assessment

GSPECT Cardio-Diagnostic Imaging(Source: www.yale.edu/imaging/)

Annualized Cardiac Events Risk

Treatment Implications(majority of patients)

<1% risk of cardiac deathand MI

Risk factor modification (RFM) in addition to current regimen

Low risk of cardiac death; Intermediate risk of MI

Aggressive RFM/medicaltreatment

Intermediate-to-high riskof both cardiac death/MI

Catheterization (possiblerevascularization)/RFM

Normal Mildly Normal Moderately / Severely Abnormal

anterior

inferior

septal lat

anterior

inferior

base apex

apex

latseptal

base

Chronic Ischemic Heart Disease treatment with complex herbal formulation Study

Roberto Guzmán, José Olalde, Francis Amendola, Oswaldo del Castillo

Results: Good response (17 out of 20 initial patients) to therapy was observed in 85% of the patients (p ≤ 6.104e-05; %=99.9999) as determined by Wilcoxon. No patient suffered adverse

events or died during the studied period.

*Results ranging between six months and one year; in first 20 out of 30 total Patients under study

One PatientDiffuse Captation

Lateral WallQualitative

20 Patients *

3 PatientsSame Perfusion Defect

Quantitative

One PatientDiffuse Captation

Inferior WallQualitative

15 PatientsPerfusion Defect

Quantitative

3 PatientsSame Captation

Lateral / Inferior WallQualitative

17 PatientsImprovement

15 Quant + 2 Qual+ + =

3 PatientsNo Improvement= =

Study Aditional Hightlights (1)

Study Aditional Hightlights (2)

PD%: 40

29 APR 2009

16 SEP2009

PD%: Post–Effort Perfusion Damage Percentage

GSPECT Image

PD%: 35

Control

6 months

Chronic Ischemic Heart Disease Six month treatment study

Funtional Capacity Time (sec)

Total452

post-treatment

386Time (sec)

pre-treatment

66Increase (sec)

6 month treatment

Patient 1

PD%: 45

13 MAY 2009

28 OCT2009

GSPECT Image

PD%: 30

Control

6 months


7 JUL2010

PD%: 15

One year

Chronic Ischemic Heart Disease One year treatment study


Patient unable to carry out the test due physical limitations

Patient 2

GSPECT Image

PD%: 20

20 MAY 2009

28 OCT2009

PD%: 10

Control

6 months


16 JUN2010

PD%: 10

One year



Total442

post-treatment

366Time (sec)

pre-treatment

76Increase (sec)

6 month treatment

Patient 3

GSPECT Image

PD%: 70

03 JUN 2009

11 NOV2009

PD%: 60

Control

6 months




Total200

post-treatment

155Time (sec)

pre-treatment

45Increase (sec)

6 month treatment

Patient 4

GSPECT Image

PD%: 30

06 MAY 2009

07 OCT2009

PD%: 25

Control

6 months

09 JUL2010

PD%: 0

One year




Total615

post-treatment

486Time (sec)

pre-treatment

81Increase (sec)

6 month treatment

48Increase (sec)

1 year treatment

Patient 5

GSPECT Image

PD%: 30

06 MAY 2009

07 OCT2009

PD%: 20

Control

6 months

09 JUN2010

PD%: 20

One year




Total662

post-treatment

553Time (sec)

pre-treatment

88Increase (sec)

6 month treatment

14Increase (sec)

1 year treatment

Patient 6

PD%: 15

29 APR 2009

16 SEP2009


GSPECT Image

PD%: 15

Control

6 months



Total609

post-treatment

555Time (sec)

pre-treatment

54Increase (sec)

6 month treatment

Patient 7

PD%: 10

14 JUL 2009

11 NOV2009

GSPECT Image

PD%: 5

Control

6 months

28 JUL2010

PD%: 5

One year




Total491

post-treatment

433Time (sec)

pre-treatment

68Increase (sec)

6 month treatment

-10Decrease (sec) 1 year treatment

Patient 8

PD%: 20

14 JUL 2009

11 NOV2009

PD%: 20

Control

6 months

04 AGO2010

PD%: 20

One year


GSPECT ImageChronic Ischemic Heart Disease One year treatment study


Total676

post-treatment

516Time (sec)

pre-treatment

132Increase (sec)

6 month treatment

28Increase (sec)

1 year treatment

Patient 9

PD%: 60

13 MAY 2009

07 OCT2009

GSPECT Image

PD%: 35

Control

6 months

02 JUN2010

PD%: 20

One year




Total428

post-treatment

339Time (sec)

pre-treatment

89Increase (sec)

6 month treatment

Patient 10

PD%: 25

12 AGO 2009

08 DEC2009


GSPECT Image

PD%: 15

Control

6 months



Total373

post-treatment

323Time (sec)

pre-treatment

50Increase (sec)

6 month treatment

Patient 11

PD%: 15

14 JUL 2009

02 DEC2009

GSPECT Image

PD%: 0

Control

6 months

04 AGO2010

PD%: 0

One year




Total570

post-treatment

432Time (sec)

pre-treatment

83Increase (sec)

6 month treatment

55Increase (sec)

1 year treatment

Patient 12

PD%: 25

23 JUL 2009

02 DEC2009


GSPECT Image

PD%: 20

Control

6 months




Patient 13

GSPECT Image

PD%: 70

11 MAR 2010

15 SEP2010

PD%: 55

Control

6 months




Total235

post-treatment

209Time (sec)

pre-treatment

26Increase (sec)

6 month treatment

Patient 14

GSPECT Image

PD%: 95

04 MAR 2010

15 SEP2010

PD%: 90

Control

6 months





Patient 15

GSPECT Image

PD%: 35

10 MAR 2010

1 SEP2010

PD%: 35

Control

6 months





Patient 16*

* Slight Qualitative Perfusion Improvement determined by diffuse radioisotope captation in lateral wall

GSPECT Image

PD%: 50

17 MAR 2010

15 SEP2010

PD%: 35

Control

6 months




Total254

post-treatment

333Time (sec)

pre-treatment

-79Decrease (sec)

6 month treatment

Patient 17

GSPECT Image

PD%: 50

17 MAR 2010

06 SEP2010

PD%: 35

Control

6 months




Total549

post-treatment

479Time (sec)

pre-treatment

70Increase (sec)

6 month treatment

Patient 18

GSPECT Image

PD%: 45

03 MAR 2010

01 SEP2010

PD%: 45

Control

6 months




Total620

post-treatment

610Time (sec)

pre-treatment

10Increase (sec)

6 month treatment

Patient 19*

* Important Qualitative Perfusion Improvement determined by diffuse radioisotope captation in inferior wall

GSPECT Image

PD%: 15

10 MAR2010

15 SEP2010

PD%: 15

Control

6 months





Patient 20

Cardiac Stent Alternatives: Associated Risk

Stem cells: Future Alternative ?

CIRCULAT IP Protection

USA Patent: Circulatory Disorders and Diabetes

Russian Patent: Method of elaboration; Circulatory Disorders and Diabetes

Mexican Patent: Circulatory Disorders and Diabetes

17 International patents (12/USA; 4/Russia; 1/Mexico)

Early results in the administration of CIRCULAT have shown it to be therapeutically efficacious, accessible and safe in the treatment of chronic ischemic heart disease.

Evidence of CIRCULAT’s efficacy was determined by state-of-the-art Gamma Single Photon Emission Computerized Tomography (GSPECT) images.

CIRCULAT is the only known orally administered treatment capable of obtaining myocardial reperfusion in chronic ischemic heart disease.

Conclusions

Next Steps

• Carry out joint phase 3 study with interested party;

• Increase numbers of patients (thirty/one hundred);

• Extend length of study (two year scenario);

• Request IP protection (in CEE) through Ischemic Cardiopathy Patent in US (PCT);

• Disseminate results of studies, seek partner and licensing and/or joint venture agreement.

Description of Circulat

Panax ginsengPfaffia paniculata

Panax quinquefolius Leuzea carthamoides

Eleutherococcus senticosus

Echinacea spp.Rhodiola rosea Grifola frondosaPetiveria alliaceaUncaria tomentosa Ganoderma lucidumSutherlandia frutescens Harpagophytum procumbens

Ginkgo bilobaHydrocotile asiaticaVaccinium myrtillus

Tabebuia avellandedae

Ruscus aculeatusAngelica sinensis Crataegus oxyacanthaHydrastis canadensisCroton lechleri

CIRCULAT is a High Pressure Liquid Chromatography fingerprinted complex formula of standardized herbal extracts, designed for circulatory disorders. Its components act synergistically

to increase the system’s survival potential (health) reducing its entropy and producing an endogenous curative tendency, without adverse effects.

CIRCULAT

Potential Synergetic Contribution

Po

ten

tial

Syn

erg

etic

Co

ntr

ibu

tio

n (

SC

)

Number of active principles (n)Number of active principles (n)

The synergetic potential of a complex herbal formulation -such as CIRCULAT- is provided by the interactions of the active principles present in each phytoceutical and can be mathematically

expressed by SC value below.

US FREE SALES CERTIFICATE

VENEZUELAN PHARMACOPEIA

GUIA SPILVA - CIRCUFORTE

VENEZUELAN FDA CERTIFICATION AS A NATURAL MEDICINE

Origin & Philosophical Background

Systemic Medicine(origin)

• Systemic Theory (ST), is published in eCAM (Oxford University Press, March, June, Sept. and Dec. 2005).

• ST stipulates that health is based on three factors:

E Functional organic energy reserve;

I Level of active biological intelligence;

O Integrity of its structure or organization.

• From ST a treatment strategy is derived denominated Systemic Medicine (SM).

• SM is a novel bio-systems approach for the treatment of chronic degenerative diseases.

• SM establishes principles for the elaboration of synergistic complex herbal formulations - such as CIRCULAT- which improve health by decreasing the body’s entropy.

Circulat187 genes

I52

E44

O14

45

OrganizationFraction

IntelligenceFraction

Common to 2 or 3 Fractions

EnergyFraction

CIRCULAT’s Synergistic -Gene Modulating- Capacity

+ + + = modulates 155 genes∑= modulates 187 genes; while ( )

The formulation modulates 32 additional genes than the sum of formulas’ individual fractions

International Publications eCAM: Part I, II and III. Systemic Theory & Systemic Medicine (2005).

eCAM: Part IV. The Praxis (2005). Investigación Clínica Sept. 2005 (vol. 46, sup. 2). Phytotherapy Research: Gene Expression (2007).

Phytotherapy Research: Diabetic Foot (2008). Phytopharm 2010 (Abstracts Book) Ischemic Cardiopathy.

http://www.scielo.org.ve/revistas/ic/eedboard.htm

CIRCULAT in Chronic Ischemic Heart Disease - 20 Pat, Diabetic Foot and Gene Expression

Health & Medicine

Transcript of CIRCULAT in Chronic Ischemic Heart Disease - 20 Pat, Diabetic Foot and Gene Expression