Compositions and methods of use of phorbol esters

A technology of phorbol ester and phorbol alcohol, applied in the composition and application field of phorbol ester

Pending Publication Date: 2018-12-11
BIOSUCCESS BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although molecular targeting has produced a variety of successful agents, multiple signaling pathways are often involved, and blocking one pathway can easily incur costs in others

Method used

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  • Compositions and methods of use of phorbol esters
  • Compositions and methods of use of phorbol esters
  • Compositions and methods of use of phorbol esters

Examples

Experimental program
Comparison scheme
Effect test

Embodiment I

[0491] Effect of TPA on peripheral white blood cell (WBC) and hemoglobin (Hb) counts in mice injected with S180 cells:

[0492] Sarcoma 180 (S180) cells were injected into Kwen-Ming mice. On day three, mice were dosed with TPA intraperitoneally (i.p.) at 50, 100 or 200 μg / kg / day for 7 days. On the second day after completion of treatment, blood samples were obtained from the tails of treated mice for WBC and Hb analysis. WBC counts in the treatment groups (50, 100 or 200ug / kg / day for 7 days) were 16.1±7.4, 18.7±.3.0 and 20.7±.3.4×10 9 / L; the WBC count of the control group was 13.6±1.8×10 9 / L. The Hb in the treatment group was 136±11, 149±12 and 149±10 g / L, and the Hb in the control group was 134+-15 g / L. The results indicated that intraperitoneal injection of TPA could increase the peripheral WBC counts of mice in a dose-dependent manner, while the Hb levels of TPA-treated mice were not much affected compared with control mice.

Embodiment II

[0494] Dose Range Studies.

[0495] TPA is given to patients by intravenous (i.v.) infusion because of the strong local irritation it produces when administered. Inject the TPA solution in a sterile syringe into 200ml of sterile saline and mix well for intravenous infusion.

[0496] Toxicity and side effects of different TPA doses administered clinically:

[0497] (1) Administer TPA at 1 mg / patient / week:

[0498] Mix 1mg TPA in the solution with 200ml sterile saline for intravenous infusion, and the intravenous infusion is completed within 1 hour at a rate of 16μg / min. One hour after TPA administration, the patient started to have chills lasting about 30 minutes, followed by fever (the patient's body temperature reached 37.5-39.5°C, lasted 3-5 hours, and then returned to normal) with varying degrees of sweating. The above symptoms can be alleviated by giving patients glucocorticoids. TPA at this dose caused a few patients to bleed, some experienced short-term dyspnea, an...

Embodiment III

[0504] First clinical study in HIV+ patients treated with TPA

[0505] Twelve symptomatic patients (five males and seven females), aged 35 to 52 years, all acquired HIV via blood transfusion in 1995 and were HIV standard were treated with TPA Refractory to treatment. Each patient was administered a body weight-adjusted dose of TPA (75 μg / sqm) in 200 ml sterile saline intravenously over 1 hour. This dose is administered once daily for the first three days of treatment. This dose was then given to each patient every other day from day 4 to day 18, followed by a 6-month rest period, after which a second course of treatment followed the same protocol.

[0506] Blood samples were collected before the first dose of TPA and on days 4 and 40 of the treatment cycle. CD3, CD4 and CD8 levels in peripheral blood were measured using monoclonal antibodies (Becton Dickson Scientific Co., Franklin Lakes, NJ) and flow cytometry (B.D. Bioscience, San Diego, CA).

[0507] As can be seen in...

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Abstract

Methods and compositions containing a phorbol ester or a derivative of a phorbol ester are provided for the treatment of chronic and acute conditions. Such conditions may be caused by disease, be symptoms or sequelae of disease. Chronic and acute conditions may be due to viral infections such as HIV and AIDS, neoplastic diseases stroke, kidney disease, urinary incontinence, autoimmune disorders, Parkinson's disease, prostate hypertrophy, aging, or the treatment of such diseases. Additional compositions and methods are provided which employ a phorbol ester or derivative compound in combinationwith at least one additional agent to yield more effective treatment tools against acute and chronic conditions in mammalian subjects.

Description

[0001] This application is a divisional application of a patent application with an application date of January 18, 2013, an application number of 201380014940.X, and a title of "phorbol ester composition and method of use". [0002] related application [0003] This application is a continuation-in-part of U.S. Patent Application Serial No. 12 / 023,753, filed January 31, 2008, which claims U.S. Provisional Patent Application Serial No. 60 / 898,810, filed January 31, 2007, filed January 18, 2012 Priority of U.S. Provisional Patent Application Serial No. 61 / 588,162 filed on January 18, 2012, U.S. Provisional Patent Application Serial No. 61 / 588,165, filed January 18, 2012, and U.S. Provisional Patent Application Serial No. 61 / 588,167, filed January 18, 2012 rights and interests, each of which is incorporated herein by reference in its entirety. technical field [0004] The present invention relates generally to the medical use of phorbol esters. Background of the invention ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/23A61P1/12A61P1/08A61P1/14A61P1/10A61P1/02A61P7/10A61P15/00A61P17/00
CPCA61K31/215A61K31/22A61K31/225A61K31/23A61K31/235A61K31/573A61K31/60A61K45/06A61K2300/00C07C2603/40A61P1/02A61P1/08A61P1/10A61P1/12A61P1/14A61P13/00A61P13/02A61P13/08A61P13/12A61P15/00A61P17/00A61P19/02A61P21/00A61P21/04A61P25/00A61P25/02A61P25/08A61P25/14A61P25/16A61P25/20A61P25/28A61P27/02A61P29/00A61P31/12A61P31/18A61P35/00A61P35/02A61P35/04A61P37/00A61P37/02A61P39/00A61P39/02A61P43/00A61P7/10A61P9/00A61P9/10A61P3/10A61K31/222A61K31/704A61K36/47C07C69/33
Inventor 韩正涛程宏峰
Owner BIOSUCCESS BIOTECH CO LTD
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