Science Group - EEC Biotech - SDT - Cancer

United States Patent Application 20100130908
Kind Code A1
Wang; Xiaohuai ; et al. May 27, 2010

METHOD OF USE OF PORPHYRINS IN PREPARING A MEDICAMENT FOR SONODYNAMIC THERAPY AND A METHOD OF SONODYNAMIC THERAPY USING PORPHYRINS

Abstract
The invention provides method of use of a porphyrin compound as shown below in preparing a medicament for sonodynamic therapy, and a method of sonodynamic therapy using a porphyrin compound. Said therapy comprises administering a porphyrin compound to a patient and applying sonic wave to the patient, ##STR00001## ##STR00002## wherein each symbol has the meaning as defined in the description.

Inventors: Wang; Xiaohuai; (Guangzhou, CN) ; Su; Jiangan; (Shanghai, CN) ; Li; Qing; (Guangzhou, CN) ; Zhao; Guanglian; (Shanghai, CN) ; Luo; Yifan; (Guangdong Province, CN) ; Yu; Bo; (Shanghai, CN)

Assignee Name and Adress: Science Group Pty. Ltd.
Victoria
AU

Serial No.: 323174
Series Code: 12
Filed: November 25, 2008

[0124]III A Clinical Case

[0125]A patient, female, 69 years old, with right breast carcinoma. 10 months after surgery and chemotherapy, a tumor metastasis was detected in liver as shows by Computed Tomography-Positron Emission Tomography (CT-PET) on Nov. 9, 2007 (see FIG. 5). The lysine form of tin chlorophyllin as indicated in the above animal test B was dissolved in 0.1 mol/L phosphate buffer (pH 7.4) and given to the patient through lingual absorption every day for 2 days. Total dose of the lysine form of tin chlorophyllin was 60 mg. After 24 h, the red light light-emitting diode (LED) was irradiated to the body surface followed by local ultrasound irradiating of the tumour area at the intensities of 2.0 W/cm.sup.2 for 20 minutes in a water bathtub every day for 3 days. One week later, the treatment was repeated. After 3 cycles of SDT treatment with the lysine form of tin chlorophyllin, CT-PET scan on Jan. 10, 2008 showed the tumor shrank and the tumor metabolic activity was inhibited (see FIG. 5). Her symptom was much improved and Blood Routine and chemistry tests showed normal result.

Source

EEC BIO-TECH (GUANGZHOU) CO., LTD (EEC Biotech), a wholly-owned subsidiary of SCIENCE GROUP PTY LTD (SG) of Australia, is a limited liability company engaged in the professional research, development and medical application of modern bio-technology, particularly in the treatment of cancer.

EEC Biotech’s Head Office is located in Guangzhou, Guangdong Province, China. On the strength of the holding company SG’s rapidly expanding global information and business network, coupled with EEC Biotech’s good relations with China’s various research and development organisations, EEC Biotech is able to quickly penetrate and develop China’s and even the global medical bio-tech market.

EEC Biotech aims to be part of the cutting-edge in the fight against cancer by funding and developing break-through medical innovations through to creatively working on patient treatment delivery.

The Company’s primary focus has been on the development of Sono-Photo Dynamic Therapy (SPDT) technology, which is a new generation of anti-tumour technology developed from Photo-Dynamic Therapy (PDT).

PDT has been widely used as an anti-tumour treatment for over 100 years. It is approved for use in many countries. SPDT uses the same theory as PDT but is more advanced and effective as it contains both sound and light activation in the process. SPDT uses a chlorophyll sensitizer, which is activated by both sound and light. SPDT is a safe, non-invasive, non-toxic treatment option that allows greater flexibility in treatment and can enhance other conventional therapies such as chemotherapy and radiation.

The Company has developed a first class leadership team dealing with research and development, promotion and marketing. At the same time, it has also sought wide-ranging cooperation with various universities and professional research institutions in Australia, America and China, giving rise to an organisation with strong multi-disciplined R & D, covering areas such as bio-technology, medicine, chemistry, physics, electronics and information technology.

The Company currently has three professional clinical R & D centres in China with one anti-cancer Research Institute approved by the Chinese Government (Shaanxi EEC Cancer Research Institute). Overseas, it also has three cooperative clinical organisations in Australia, America and the United Kingdom. It is a corporate member of the Guangzhou Anti-Cancer Association, the Shaanxi Anti-Cancer Association and the American Society of Clinical Oncology.

EEC Biotech possesses several globally-leading patented technologies on cancer treatment, both within and without China.

Source

Sonodynamic Therapy (SDT)

The photodynamic agent we use is also sensitive to ultrasound frequencies. This approach allows deeper penetration into the body. Sonodynamic therpay is carried out using a simple therapeutic ultrasound machine with especially designed treatment head known as maniple, which is applied over the affected area with some ultrasound gel placed on the skin. This is done after the light bed exposure.

We are combining Photodynamic therapy with Sonodynamic therapy. This uses low-level ultrasound, which kills cancer cells using a non-thermal effect, especially cavitation. The agent we use is sensitive to the ultrasound frequency we use, which is 1 Mhz. Following the light bed exposure (Photodynamic Therapy), the ultrasonic probe, covered with ultra sound gel, is moved over the skin on the area nearest to the main tumour mass. The use of ultrasound enables us to penetrate significantly deeper into the body than we would otherwise be able to do. (see a review of research into the uses of low level ultra sound in cancer therapy, Uyu, Wang & Mason in Ultra Sonics Sonochermistry, Vol 11, issue 2, April 2004, pages 95-130).

Most photosensitizers come from a class of naturally occuring compounds called porphorins. Natural porphorins are breakdown products from recycled haemoglobin and are inherently light sensitive. These accumulate in tumours and cause cancer cells to auto-fluoresce. The first generation of photosensitizer approved for use in cancer treatment - Photofrin, - is derived from haemoglobin, whilst some of the more advanced agents are chlorophyll derivatives.

PDT has several advantages over surgery and radiotherapy; it is comparatively non-invasive, it can be targeted accurately and repeated dosages can be given without the total dose limitations associated with radiotherapy, and the healing process results in little or no scarring. PDT can always be done on an out-patient or day case setting, and it has no side serious effects.

The next generation of Photodynamic Therapy is a significant advance on previous PDT. This uses a specific extract of Chlorophyll A (trade name Ausclorin) which does not have to be given intravenously and can be given orally. It accumulates selectively in tumour sites and it does not persist in the skin. Photofrin does persist, so long term photosensitivity can develop lasting as long as 90 days. With the new preparation, the agent is cleared from the skin within 24 to 48 hours, so no photosensitivity occurs. Ausclorin and previous photosensitizers can use the laser, or a specialised light consisting of light emitting diodes, emitting in the red light region and the infra-red region of the spectrum or with light beds using fluorescent tubes in the red light region for whole body treatment.. Because the breakdown wave lengths of Ausclorin also occur in the infra-red region, this means that with the infra-red lights, penetration can occur as deep as twelve inches into the body, so deep tumours can be treated from the surface. This therefore makes it a non-invasive whole body treatment. The treatment programme can be repeated as often as is necessary, and for advanced tumours it is best to treat slowly so as to avoid too rapid a tumour break down in too short a period of time.

METHOD OF TREATMENT USING SONODYNAMIC THERAPY (SDT) AND AUSCLORIN PHOTODYNAMIC THERAPY (PDT):

The patient is assessed clinically. Then a dose of Ausclorin is calculated based on the patient's weight and stage of the tumour. This is taken orally each morning before breakfast whilst the Ausclorin clears from the skin and accumulates selectively in tumour sites. Following this the patient is exposed to the appropriate lights. The time of exposure is important, and can vary from up to 60 minutes for patients with less advanced tumours, to only a few minutes with patients with more advanced tumours (the more advanced the tumour, the slower the treatment programme).

Further light bed exposure is then calculated on an on-going clinical basis. The patient is given enough Ausclorin for treatment at the clinic and three months treatment at home.

Anecdotally there has been success using PDT with breast cancer and prostate cancer. There have been encouraging results with several types of brain tumour including glioblastoma multiforme, and many brain tumours significantly regressed during photodynamic therapy. One case of glioblastoma multiforma showed a total dissappearance of tumour.

We often combine ozone autohaemotherapy with PDT. PDT relies on the production of singlet oxygen (O). This is derived from oxygen (O2). Tumours are characteristically hypoxic (showing low oxygen lavels). Ozone autohaemotherapy is an effective way of increasing oxygenation just before light bed exposure, therefore increasing the effectiveness of PDT.

SCIENTIFIC INFORMATION REGARDING NEXT GENERATION PHOTODYNAMIC THERAPY

The fluorescent camera can display tumours near the surface of the body. This is often as good as, if not better than the latest scans known as PET scans (position emission tomography).

BRIEF SUMMARY OF RESULTS FOR TEN RECENT CONSECUTIVE PATIENTS IN A COLLEAGUES CLINIC WHO HAS USED SDT OVER THE PAST 12 MONTHS:

1. Stage III breast cancer. Primary breast tumour plus metastases in the axillary lymph node, the other breast and the liver. After PDT and lumpectomy: no evidence of cancer in all four sites.

2. Stage IV breast cancer with rampant body metastases. Very low energy, not enough to work in the garden. In bed by 7:30pm. After PDT (ongoing) weight increased 3kg and now normal. Normal sleeping time and energy levels. Resumed gardening. Scan shows that the tumours have stopped spreading.

3. Metastatic melanoma grade IV. ABout 80 metastases visible. Oncologist predicted 2 more months of life. After PDT (ongoing), Alive and well 4 months after prediction. Metastases down to about 20. Energy, appetite and weight improved. Physician estimates that about 80% of the cancer is gone. Further treatment needed.

4. Prostate cancer (large tumolur mass), grade IV, urinary infections, bowel infections, Inability to urinate without catheter, impotent. After SDT/PDT (ongoing) Prostate shrinking and softening, urination better, impotence easing. Needs further treatment but improving.

5. Ovarian cancer Grade IV. Had hysterectomy and other surgery. No symptoms other than elevated cancer marker. After pDT cancer marker now normal. No evidence of cancer.

6. Squamous cell carcinoma grade 1. Lump on upperlip removed surgically. PDD showed 6 metastases on upper lip. After SDT all metastases have disappeared..

7. Prostate grade IV. Hard prostate with 2 nodules, metastasized outside the gland. After SDT (ongoing) Prostate shrunk, softened, one nodule disappeared. Better urination. Clear or almost clear of cancer.

8. Mesothelioma lung cancer. Symptoms include coughing at night, disturbed sleep. Painful breathing, not allowing deep inhalations. Photodynamic diagnosis showed over 12 metastases in the thorax. No noticable benefits from chemotherapy. After SDT (ongoing): Coughing at night has stopped, giving much better sleep. Breathing not as painful, allowing deeper inhilation. "I have an amazing increase in energy". Visible metastases have dropped from 12 or more to one.

9. Breast cancer grade IV. Lumpectomy. PDD showed metastases in the breast and the axillary lymph nodes. After SDT (ongoing) Cleared metastases from the breast. Those in the lymph glands remain. Next treatment will be PDT/SDT.

10. Breast cancer grade IV with extensive liver metastases. PDT failed to hault the progress of the illness. SDT was not available at the time and she has chosen other treatment.

Source

Ausclorin

(WO/2009/026724) SYSTEM AND APPARATUS FOR SONODYNAMIC THERAPY

Biblio. Data

• Description
• Claims
• National Phase
• Notices
• Documents

Pub. No.: WO/2009/026724 International Application No.: PCT/CA2008/001548 Publication Date: 05.03.2009 International Filing Date: 29.08.2008
IPC:	A61N 7/00 (2006.01)
Applicants:	ANGEL SCIENCE & TECHNOLOGY (CANADA), INC. [CA/CA]; 4936 Yonge Street, Suite 260, Toronto, ON M2N 6S3 (CA) (All Except US). CHEN, Rixin [CA/CA]; (CA) (US Only).
Inventor:	CHEN, Rixin; (CA).
Agent:	DEETH WILLIAMS WALL LLP; 400-150 York Street, Toronto, Ontario M5H 3S5 (CA).
Priority Data:	11/849,179 31.08.2007 US

Title:

SYSTEM AND APPARATUS FOR SONODYNAMIC THERAPY >>>>>>>>>>>>>>>>>>>>>>>>>>>>>Click pic to enlarge

Abstract:

The present invention relates to diffuse ultrasound along with chemical agents to treat tissue, called sonodynamic therapy (SDT), and a system for treatment using SDT that comprises a whole body ensonification apparatus and control system. The whole body ensonification may reduce the chances of missing desired tissue that may not be easily detectable or may be found throughout the body. The apparatus has a plurality of diffuse ultrasound transducers for ensonifying at least part of a chamber filled with fluid and designed to accommodate a body for treatment. The person may be treated with sono-sensitive chemical agents, which may be activated when ensonified by the apparatus.

Source

US Filing

United States Patent Application	20090062724
Kind Code	A1
Chen; Rixen	March 5, 2009

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SYSTEM AND APPARATUS FOR SONODYNAMIC THERAPY

Abstract

The present invention relates to diffuse ultrasound along with chemical agents to treat tissue, called sonodynamic therapy (SDT), and a system for treatment using SDT that comprises a whole body ensonification apparatus and control system. The whole body ensonification may reduce the chances of missing desired tissue that may not be easily detectable or may be found throughout the body. The apparatus has a plurality of diffuse ultrasound transducers for ensonifying at least part of a chamber filled with fluid and designed to accommodate a body for treatment. The person may be treated with sono-sensitive chemical agents, which may be activated when ensonified by the apparatus.

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Inventors:

Chen; Rixen; (Vancouver, CA)

NOTES:
ANGEL SCIENCE & TECHNOLOGY (CANADA), INC.

Angel’s HIFU technology has been developed in conjunction with the China National Ultrasound Research Laboratory and the technology continues to be expanded and improved by its researchers and scientists today. Angel began first stage clinical trials in China in 2002. Successful and positive third stage clinical trials were completed at the end of 2005.
Source

Photodynamic and Sonodynamic Therapy, Experiences with a Novel Approach

JNK/Ak
Masters/JNK Papers/ Photodynamic and Sonodynamic Therapy – A Novel Approach
October 2007

Photodynamic and Sonodynamic Therapy, Experiences with a Novel Approach.

Introduction

I have been asked to write a paper on our experiences and methods and also results, in our use of a novel approach to Photodynamic Therapy. This is something we have been developing for several years, together with two other clinics, Dr X Wang, Chief of Oncology Department, Friendship Hospital, Guangzhou, China and also the Opal Clinic, Melbourne, Australia under the direction of Dr Douglas Mitchell. The reason why all three clinics developed this approach is that we are all faced with late stage cancer patients who have been through all the conventional treatment modalities, and are practically all metastatic cancers. We therefore have an interest in a safe approach to tumour cell destruction, however in all of these patients the approach is fundamentally palliative. Our results have been encouraging leading to relevant conclusions outlined in the last section of this paper. Over the past three years our clinic (The Dove Clinic for Integrated Medicine) has treated over 80 patients, the Opal Clinic has treated slightly less, and Dr Wang in Guangzhou has treated more than this number. This paper is not a formal clinical trial, it is a preliminary report. I therefore thought it best to discuss five cases fairly typical of the kind of cases on which we use this palliative approach. The use of our novel approach centres around the development of a specific sensitizer (Sonalux 1) this is a highly purified mixture of several chlorins, each with a different side chain. This agent has been shown to break down at 636 nanometres and also to be sensitive to ultrasound.
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Source

Thomas J. Lewis, PhD

17^th Annual World Congress on Anti-Aging Medicine

23 - 25 April 2009 Orlando, FL, USA

16^th Annual World Congress on Anti-Aging Medicine

11 - 14 December 2008 Las Vegas, Nevada, USA

Thomas J. Lewis, PhD

Dr. Thomas J. Lewis holds a Ph.D. in Inorganic and Physical Chemistry from MIT (1984). His research career focused mainly on kinetics and electron transfer properties of metal centered macrocycles. He has consulted in toxicology to much of big Pharma. Recently he developed several new sonodynamic therapeutic agents for cancer treatment.

Source 1

Source 2

Primary clinical use of sonodynamic therapy (SDT) for advanced breast cancer

Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 12029
© 2008 American Society of Clinical Oncology

Abstract

X. J. Wang, D. Mitchell and T. J. Lewis

Liu Hua Qiao Hospital, Boston, MA; Opal Clinic, Victoria, Australia; SonneMed, LLC, Boston, MA

12029

Background: There are increasing data showing that sonodynamic therapy (SDT), which refers to a synergistic effect of drugs and ultrasound, is a promising new modality for cancer treatment. Recently a new sonosensitizing agent has been developed by SonneMed, LLC. It is extremely sensitive to ultrasound. As with photodynamic sensitizers, it is specifically absorbed into tumor cells and produces singlet oxygen upon interaction with the right frequency and intensity of ultrasound. The singlet oxygen is able to create cellular necrosis. Our animal studies showed that SDT with SF1 inhibits growth of mouse S-180 sarcoma. Here we report initial clinical data using SDT with SF1 for advanced breast cancer. Methods: Three patients with metastasized pathologically proven breast carcinoma were studied. Their carcinoma failed to respond to conventional therapy and spread to the whole body. The SDT agent was provided through lingual absorption. After 24h, light and ultrasound was applied, irradiating the tumour area for 20 minutes daily for 4 days and repeated every two weeks. Results: Case 1 had breast carcinoma which spread to the whole body. She had surgery, chemo, RT, hormone, Herceptin, Zometa etc, but all failed. The tumor kept growing until she multiple acute symptoms. After 3 SDT treatments her symptom improved significantly and windpipe spile, gastric and urine catheter were all taken off. PET/CT scans showed a positive partial result (PR). Case 2 had left breast carcinoma with multi-organ metastases. After 2 treatments PET/CT scan showed very positive PR. PET/CT taken 28 months after treatment showed no signs of tumor in any cavity of the body. Case 3 had left breast carcinoma. All conventional treatments failed. Her carcinoma metastases broadly and her marrow function was very poor. After 2 cycle treatments PET/CT scan showed PR. Conclusions: Primary clinical data shows that SDT with SF1 is well tolerated and has a significant therapeutic effect for some patients with advanced breast cancer. Even a terminally ill patient can be treated safely and effectively. Sonodynamic therapy with SF1 has significant merit for further investigation.

No significant financial relationships to disclose.

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