GB2126082A - Pharmaceutical preparations having analgetic and cytostatic activity - Google Patents
Pharmaceutical preparations having analgetic and cytostatic activity Download PDFInfo
- Publication number
- GB2126082A GB2126082A GB08321595A GB8321595A GB2126082A GB 2126082 A GB2126082 A GB 2126082A GB 08321595 A GB08321595 A GB 08321595A GB 8321595 A GB8321595 A GB 8321595A GB 2126082 A GB2126082 A GB 2126082A
- Authority
- GB
- United Kingdom
- Prior art keywords
- fatty acids
- esters
- ketonic
- short
- pharmaceutical preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
Abstract
The invention relates to the use of short-chain fatty acids, hydroxy fatty acids and ketonic fatty acids, their salts and esters, as analgesics. The invention also relates to pharmaceutical preparations with cytostatic activity which are characterized in that they contain esters of short-chain fatty acids and/or hydroxy fatty acids and/or ketonic fatty acids.
Description
SPECIFICATION
Pharmaceutical preparations having analgetic and cytostatic activity
This invention relates to pharmaceutical preparations having analgetic activity. Analgesics are nowadays divided into so-called weak analgesics which are used for everyday pain and for the treatment of inflammation and fever etc., this category including salicylic acid derivatives, pyrazolone derivatives, dioxyopyrazolidine and more recently also indolyl acetic acid derivatives.
The degree of effectiveness of these compounds is not generally adequate to provide relief from conditions producing severe or very severe pain. In these cases use is made of the so-called strong analgesics, these being derived predominantly from morphine, or belonging to the pethidine, methadone, morphinane or benzomorphane groups. Unfortunately it is common to all strong analgesics to a greater or lesser degree that they have, in addition to the analgesic effect, a number of side effects which may make their use problematic in some cases, such as, for example, by causing depression of respiration and the like.
The principal side effect is that these very strong compounds -- in accordance with the condition of the patient in each case - cause addiction phenomena which vary in degree and rapidity such that their use for long-term disorders is problematic for this reason. There has therefore up to now been an urgent need for the development of strong analgesics which are not addictive. The present invention therefore aims to develop a new strong analgesic.
The invention also relates to pharmaceutical preparations having cytostatic activity. Cancer cells are produced by the transformation of endogenous cells. Although the cause which triggers their spontaneous development is unknown, it is at present assumed that they may be caused predominantly by exogenous noxious agents, virus infections or by the sudden "growth" of a cancer-specific gene already present in the cell. The malignancy of the cancer cells is shown by their autonomy of growth, ie. by their ability to grow and infiltrate in an unrestricted and unintegrated manner the structure of the organs with the destruction of tissue.
Endless and frequently contradictory data is available with respect to the metabolism of tumours. This is partly due to the fact that it is extremely difficult to speak of a tumour-specific metabolism. A feature of malignant tumours which is often observed is their high glycolysis and their low oxygen absorption, which - in contrast to body tissue which has grown normally - is also maintained in the case of adequate oxygen supply. In the case of the treatment of tumours by chemotherapy it is attempted to utilize the differences in metabolism between cancer cells and normal cells in order to achieve selective destruction of the cancer cells. Up to now use has preferably been made of inhibitors produced by the biosynthesis of purines, nucleic acids and proteins.Their effect is chiefly based on the relatively high rate of mitosis of the cancer cells, so that simultaneous damage to normal cells, in particular those with a high mitosis frequency, must be taken into account. The invention therefore also aims to develop a further agent for controlling malignant growth which attacks specific degenerate cells and has as little effect as possible on normal cells.
The present invention in one aspect provides a pharmaceutical preparation having an analgesic effect, which contains one or more short-chain fatty acids and/or hydroxy fatty acids and/or ketonic fatty acids.
The pharmaceutical preparation may suitably contain one or more of esters of short-chain fatty acids and/or hydroxy fatty acids and/or ketonic fatty acids, in particular one or more of (i) butyric acid esters; (ii) glycerin-terbutyric acid esters; (iii) ,8-hydroxybutyric acid esters; (iv) aceto-acetic acid esters.
Short-chain fatty acids, and in particular butyric acid, are occasionally used in pharmacy as agents for the local treatment of warts, and in addition butyric acid and sodium butyrate have been proposed for external use in the cleansing of tumorous growths. The analgesic effect of shortchain fatty acids, hydroxy fatty acids or ketonic fatty acids has, however, never been described before. It has now been surprisingly shown that a strong analgesic effect is produced when these compounds are administered intravenously, which effect also continues for a relatively long period.
Side effects have not been observed in the treatment tests carried out up to now, with the exception of a certain sedative effect.
In accordance with the invention, either the salts of the fatty acids or in particular the esters are used, as these are osmotically inactive and may be assimilated at the required amount into sufficiently stable pharmaceutical products. In the case of esters which dissolve with difficulty, preparation may be carried out with physiologically harmless emulsifiers. The dosage is approximately 200 mMol-1 000 mMol in 24 hours.
The acids and acid esters used in accordance with the invention are known per se and may be produced in accordance with the conventional methods for the synthesis of carbonic acids, hydroxycarbonic acids and ketocarbonic acids or their esters. A laevorotatory p-hydroxybutyric acid may be obtained, for example, in accordance with the method disclosed in the German Patent
Specification 27 33 202. Use is preferably made of those compounds which are particularly suitable for the production of intravenous pharmaceutical preparations as a result of their stability, osmotic inactivity etc. Use is preferably made, for the ester, of compounds in which the alcohol proportion is physiologically harmless or even metabolic such as, for example, glycerin ester.
The production of the pharmaceutical preparations is carried out in a manner known per se, if necessary with the addition of emulsifiers in the case of esters which are difficult to dissolve such as, for example, with the use of lecithin, mixed acid triglycerides and the like.
The invention in another aspect provides a pharmaceutical preparation having a cytostatic effect, which contains one or more esters of shortchain fatty acids and/or hydroxy fatty acids and/or ketonic fatty acids.
The pharmaceutical preparation may suitably contain one or more of (i) butyric acid esters; (ii) glycerinterbutyric acid esters; (iii) ss-hydroxybutyric acid esters; (iv) aceto-acetic acid esters.
The starting point for the development of this aspect of the present invention was the empirically ascertained fact that cancerous disorders respond to the so-called insulin-diet treatment. In this the patient receives a low carbohydrate diet and simultaneous doses of insulin. This frequently produces a dramatic reduction of the tumour growth and may lead to complete macroscopic remission, although in some cases the blood sugar level may not be so readily reduced. Patients with tumours show a remarkably high lack of sensitivity to the administration of insulin. It can be assumed that the glycolytic enzymes in tumours obey the same regulation mechanisms as in normal cells. It has also been observed that the tumour cells waste a large amount of glucose on account of the low degree of efficiency of zymosis.As the mutual regulatory interdependence between carbohydrate metabolism and fat metabolism is known, the glycolysis may be reduced to minimum values in the entire organism in this respect by displacement. This should have a particularly strong effect on the tumour, since tumours with increasing malignity of growth are always dependent on the recovery of energy from the glycolysis, as their escape routes to other substrates and metabolic paths are increasingly lost.The glucose-saving effect of fatty acids and ketone bodies has already been measured in all respects, and it is therefore known that fatty acids and ketone bodies considerably reduce the activity of the glycolytic key enzymes, and in addition the activity of glucose-6-phosphate-dehydrogenase and 6-phospho-gluconate-dehydrogenase are reduced in the hexosemonophosphate shunt, such that there is a relative lack of ribose for DNA synthesis, which again leads to a lack of NAD and therefore to a bottleneck in glycolysis as a result of the prevention of hydrogen transport. In summary, this means that the starvation of a tumour must be possible in that the body is brought for a certain period of time into a metabolic position -- which is otherwise always considered to be fatal from the medical point of view - which is strongly ketoacidotic.
Particularly suitable for the production of an exogenous ketoacidosis are short-chain fatty acids such as, for example, butyric acid and propionic acid or the endogenous decomposition products produced by ,B-oxidation such as the corresponding hydroxy and ketoacids such as, for example, J3-hydrnxybuwric acid or aceto-acetic acid.
Butyric acid has already been proposed in 1933 by J. Watson, "The Lancet" ii 618: 746-748 for the treatment of tumours, although only for external use in the cleansing of tumorous growths. In more recent times, comparative tests have been carried out on the effect of butyric acid on metabolic processes, and H. Barker et al., in
Br. J. Cancer (1 977), 35, 314, for example, report on the effect of sodium butyrate on the proliferation of malignant trophoblasts in culture tests. In laboratory tests butyric acid and sodium butyrate have also been investigated with respect to their
effect on malignant cells, for example Leavitt
et al., Nature 271 (5642) 262-265, 1978 or
M. F. Bourgeade et al. in Cancer Research 39, 4720-4723, November 1979.As far as is known, these acids or their alkaline salts have scarcely been used clinically up to now and our own tests have shown that there is little possibility of clinical use. Oral administration of the acid or the salt is not therefore very promising, as shortchain fatty acids are very substantially broken down after a single passage through the liver, such that the majority of the compounds have already been eliminated before a sufficient concentration may be obtained in the surrounding area. The intravenous administration of shortchain fatty acids, hydroxy fatty acids and ketonic fatty acids is opposed by the fact that this is not possible on account of the dosage to be administered and consequently the pH value. Our own tests have shown that minimum dosage of 200 mMol-1 000 mMol of acid is required.If this amount is used in the salt form, the body is flooded with equimolar cations, chiefly sodium or potassium, with the known consequences resulting from this.
Intravenous administration of the compound is therefore only possible in the manner proposed by the invention, in which the esters are used, as these are osmotically inactive and may be assimilated at the required amount into adequately stable pharmaceutical preparations. In the case of esters which are difficult to dissolve, assimilation may be carried out together with physiologically harmless emulsifiers. In the usage of the invention, the ketogenic fatty acid esters are administered exclusively by intravenous methods, at amounts of approximately 200 mMol--1000 mMol in 24 hours.
The acid esters used in accordance with the invention are known per se and may be produced by the conventional methods for the synthesis of carbonic acids, hydroxy-carbonic acids and ketocarbonic acids and their esters. A laevorotatory ,B-hydroxybutyric acid may be obtained, for example, from the method disclosed in the German Patent Specification 27 33 202.
Use is preferably made of compounds of this type which are particularly suitable for the production of intravenous pharmaceutical preparations as a result of their stability, their osmotic inactivity etc.
This includes butyric acid esters, P-hydroxybutyric acid esters and aceto-acetic acid esters. For the ester use is preferably made of compounds in which the alcohol proportion is physiologically harmless or even metabolic such as, for example, glycerin ester.
The production of the pharmaceutical preparations takes place in a manner known per se, possibly with the addition of emulsifiers to the esters, which are osmotically inactive although difficult to dissolve in water such as acid triglycerides mixed with the lecithin or the like. An injection or infusion unit as a rule contains approximately 400 mMol of active substance, the infusion taking place over a period of approximately 2 hours.
The invention will be further described with reference to the following illustrative Examples.
EXAMPLE 1
35.0 g of glycerin-terbutyric acid ester and 9.55 g of lecithin were dissolved in 33.0 g of isotonic phosphate buffer and homogenized in a homogenizer. The homogenous product was placed in conventional injection phials and sterilized in the normal way.
EXAMPLE 2 (analgetic activity)
The infusion solution described in Example 1 was tested clinically on conditions of very severe pain. In the case of a patient with bone metastasis after mastocarcinoma, who had up to then been receiving very high doses of analgesic, the pain was completely relieved for 24 hours by an infusion. In the case of further patients with carcinoma of the colon who had been treated by radiology and chemotherapy, the administration of very strong analgesics could be decreased to two or three hour gaps after they had received several infusions of the solution described in Example 1.
Even in the case of patients with multiple metastasis after carcinoma of the prostate it was possible to decrease the need for analgesics by 90% after the second infusion, as the patient felt hardly any pain. The effect of the infusion and the pain relief obtained thereby lasted approximately 2 days, after which the next infusion had to be administered.
EXAMPLE 3 (cytostatic activity)
Up to now clinical tests have been carried out on approximately 40 patients considered to be incurable. The treatment took the form of a daily dose of approximately 35 g butyric acid ester.
During the treatment it was particularly striking that the sudden pain relief provided even after the first infusion was so marked that even patients who had been receiving very strong analgesics
ad lib. no longer required these. After a few
infusions there was a clear improvement in general condition and an increase in bodily and mental activity.
Claims (11)
1. A pharmaceutical preparation which contains one or more short-chain fatty acids and/or hydroxy fatty acids and/or ketonic fatty acids.
2. A pharmaceutical preparation which contains one or more esters of short-chain fatty acids and/or hydroxy fatty acids and/or ketonic fatty acids.
3. A pharmaceutical preparation as claimed in
Claim 2, which contains one or more butyric acid esters.
4. A pharmaceutical preparation as claimed in
Claim 2, which contains one or more glycerinterbutyric acid esters.
5. A pharmaceutical preparation as claimed in
Claim 2, which contains one or more ,B-hydroxybutyric acid esters.
6. A pharmaceutical preparation as claimed in
Claim 2, which contains one or more aceto-acetic acid esters.
7. A pharmaceutical preparation which contains one or more short-chain fatty acids and/or hydroxy fatty acids and/or ketonic fatty acids, together with a pharmaceutical carrier or diluent.
8. A pharmaceutical preparation which contains one or more esters of short-chain fatty acids and/or hydroxy fatty acids and/or ketonic fatty acids, together with a pharmaceutical carrier or diluent.
9. A pharmaceutical preparation according to
Claim 1 or 2, substantially as herein described in any of the foregoing Examples.
1 0. One or more short-chain fatty acids and/or hydroxy fatty acids and/or ketonic fatty acids, for use in analgesic treatment.
11. One or more esters of short-chain fatty acids and/or hydroxy fatty acids and/or ketonic fatty acids, for use in analgesic treatment.
1 2. One or more esters of short-chain fatty acids and/or hydroxy fatty acids and/or ketonic fatty acids, for use in cytostatic treatment.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19823229955 DE3229955A1 (en) | 1982-08-12 | 1982-08-12 | Pharmaceutical compositions with analgesic action |
DE19823229956 DE3229956A1 (en) | 1982-08-12 | 1982-08-12 | Pharmaceutical compositions with cytostatic action |
Publications (2)
Publication Number | Publication Date |
---|---|
GB8321595D0 GB8321595D0 (en) | 1983-09-14 |
GB2126082A true GB2126082A (en) | 1984-03-21 |
Family
ID=25803698
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB08321595A Withdrawn GB2126082A (en) | 1982-08-12 | 1983-08-11 | Pharmaceutical preparations having analgetic and cytostatic activity |
Country Status (2)
Country | Link |
---|---|
AU (1) | AU1795383A (en) |
GB (1) | GB2126082A (en) |
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH01299222A (en) * | 1988-05-26 | 1989-12-04 | Otsuka Pharmaceut Factory Inc | Antitumor agent |
EP0731712A1 (en) * | 1993-10-29 | 1996-09-18 | Trustees Of Boston University | Physiologically stable compositions of butyric acid, and butyric acid salts and derivatives as anti-neoplastic agents |
EP0780123A1 (en) * | 1995-12-01 | 1997-06-25 | Shimizu Pharmaceutical Co., Ltd. | Beta-hydroxybutyric acid or acetoacetic acid or salts or esters therof for use in improving cerebral function |
US5939455A (en) * | 1997-03-11 | 1999-08-17 | Beacon Laboratories, Inc. | Therapeutic augmentation of oxyalkylene diesters and butyric acid derivatives |
US6011000A (en) * | 1995-03-03 | 2000-01-04 | Perrine; Susan P. | Compositions for the treatment of blood disorders |
US6030961A (en) * | 1997-03-11 | 2000-02-29 | Bar-Ilan Research & Development Co., Ltd. | Oxyalkylene phosphate compounds and uses thereof |
US6043389A (en) * | 1997-03-11 | 2000-03-28 | Mor Research Applications, Ltd. | Hydroxy and ether-containing oxyalkylene esters and uses thereof |
US6110955A (en) * | 1997-03-11 | 2000-08-29 | Beacon Laboratories, Inc. | Metabolically stabilized oxyalkylene esters and uses thereof |
US6110970A (en) * | 1997-03-11 | 2000-08-29 | Beacon Laboratories, Inc. | Nitrogen-containing oxyalkylene esters and uses thereof |
US6124495A (en) * | 1997-03-11 | 2000-09-26 | Beacon Laboratories, Inc. | Unsaturated oxyalkylene esters and uses thereof |
US6130248A (en) * | 1996-12-30 | 2000-10-10 | Bar-Ilan University | Tricarboxylic acid-containing oxyalkyl esters and uses thereof |
US6207856B1 (en) | 1997-03-17 | 2001-03-27 | Btg International Limited | Therapeutic compositions |
US6316038B1 (en) | 1997-03-17 | 2001-11-13 | Btg International Limited | Therapeutic compositions |
AU749638B2 (en) * | 1997-03-17 | 2002-06-27 | Btg International Limited | Therapeutic compositions |
US7485743B2 (en) | 2004-07-20 | 2009-02-03 | Btg International Limited | Oligomeric ketone compounds |
US7910624B1 (en) | 1995-03-03 | 2011-03-22 | The Trustees Of Boston University | Compositions for the treatment of blood disorders |
US8242172B2 (en) | 1998-02-11 | 2012-08-14 | Trustees Of Boston University | 2,2-dimethylbutyric acid oral pharmaceutical compositions |
US8618068B2 (en) | 2009-12-08 | 2013-12-31 | Trustees Of Boston University | Methods and low dose regimens for treating red blood cell disorders |
US8993581B2 (en) | 2009-09-24 | 2015-03-31 | Trustees Of Boston University | Methods for treating viral disorders |
WO2020127182A1 (en) * | 2018-12-18 | 2020-06-25 | Société des Produits Nestlé S.A. | Mixed triglyceriges |
US10857152B2 (en) | 2010-03-11 | 2020-12-08 | Trustees Of Boston University | Methods and compositions for treating viral or virally-induced conditions |
US10953011B2 (en) | 2019-05-31 | 2021-03-23 | Viracta Therapeutics Inc. | Methods of treating virally associated cancers with histone deacetylase inhibitors |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8105809B2 (en) | 2008-07-03 | 2012-01-31 | Accera, Inc. | Enzymatic synthesis of acetoacetate esters and derivatives |
Citations (6)
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---|---|---|---|---|
GB490942A (en) * | 1937-02-23 | 1938-08-23 | Ig Farbenindustrie Ag | Process for the manufacture of highly concentrated solutions of fat soluble hormones and derivatives thereof |
GB584497A (en) * | 1944-04-17 | 1947-01-16 | Winifred Mercer Pitkin | Therapeutic preparations for intramuscular and subcutaneous injection and methods of making the same |
GB779965A (en) * | 1954-05-26 | 1957-07-24 | Bayer Ag | Growth promoting feeding stuffs |
GB1304137A (en) * | 1970-09-26 | 1973-01-24 | ||
GB1542028A (en) * | 1976-08-04 | 1979-03-14 | Agroferm Ag | Microbiological method of manufacturing d(-)-3-hydroxybutyric acid |
GB1582992A (en) * | 1976-07-28 | 1981-01-21 | Procter & Gamble | Intravenous solutions with an antimicrobial agent |
-
1983
- 1983-08-11 GB GB08321595A patent/GB2126082A/en not_active Withdrawn
- 1983-08-12 AU AU17953/83A patent/AU1795383A/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB490942A (en) * | 1937-02-23 | 1938-08-23 | Ig Farbenindustrie Ag | Process for the manufacture of highly concentrated solutions of fat soluble hormones and derivatives thereof |
GB584497A (en) * | 1944-04-17 | 1947-01-16 | Winifred Mercer Pitkin | Therapeutic preparations for intramuscular and subcutaneous injection and methods of making the same |
GB779965A (en) * | 1954-05-26 | 1957-07-24 | Bayer Ag | Growth promoting feeding stuffs |
GB1304137A (en) * | 1970-09-26 | 1973-01-24 | ||
GB1582992A (en) * | 1976-07-28 | 1981-01-21 | Procter & Gamble | Intravenous solutions with an antimicrobial agent |
GB1542028A (en) * | 1976-08-04 | 1979-03-14 | Agroferm Ag | Microbiological method of manufacturing d(-)-3-hydroxybutyric acid |
Cited By (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH01299222A (en) * | 1988-05-26 | 1989-12-04 | Otsuka Pharmaceut Factory Inc | Antitumor agent |
EP0731712A1 (en) * | 1993-10-29 | 1996-09-18 | Trustees Of Boston University | Physiologically stable compositions of butyric acid, and butyric acid salts and derivatives as anti-neoplastic agents |
US5858365A (en) * | 1993-10-29 | 1999-01-12 | Trustees Of Boston University | Methods for the treatment of wounds using butyric acid salts and derivatives |
EP0731712A4 (en) * | 1993-10-29 | 2005-11-09 | Univ Boston | Physiologically stable compositions of butyric acid, and butyric acid salts and derivatives as anti-neoplastic agents |
US6011000A (en) * | 1995-03-03 | 2000-01-04 | Perrine; Susan P. | Compositions for the treatment of blood disorders |
US7910624B1 (en) | 1995-03-03 | 2011-03-22 | The Trustees Of Boston University | Compositions for the treatment of blood disorders |
EP0780123A1 (en) * | 1995-12-01 | 1997-06-25 | Shimizu Pharmaceutical Co., Ltd. | Beta-hydroxybutyric acid or acetoacetic acid or salts or esters therof for use in improving cerebral function |
US6232345B1 (en) | 1995-12-01 | 2001-05-15 | Shimizu Pharmaceutical Co., Ltd. | Cerebral function improving agents |
US6136862A (en) * | 1995-12-01 | 2000-10-24 | Shimizu Pharmaceutical Co., Ltd. | Cerebral function improving agents |
US6130248A (en) * | 1996-12-30 | 2000-10-10 | Bar-Ilan University | Tricarboxylic acid-containing oxyalkyl esters and uses thereof |
US5939455A (en) * | 1997-03-11 | 1999-08-17 | Beacon Laboratories, Inc. | Therapeutic augmentation of oxyalkylene diesters and butyric acid derivatives |
US6124495A (en) * | 1997-03-11 | 2000-09-26 | Beacon Laboratories, Inc. | Unsaturated oxyalkylene esters and uses thereof |
US6110970A (en) * | 1997-03-11 | 2000-08-29 | Beacon Laboratories, Inc. | Nitrogen-containing oxyalkylene esters and uses thereof |
US6110955A (en) * | 1997-03-11 | 2000-08-29 | Beacon Laboratories, Inc. | Metabolically stabilized oxyalkylene esters and uses thereof |
US6043389A (en) * | 1997-03-11 | 2000-03-28 | Mor Research Applications, Ltd. | Hydroxy and ether-containing oxyalkylene esters and uses thereof |
US6239176B1 (en) | 1997-03-11 | 2001-05-29 | Beacon Laboratories, Inc. | Uses of hydroxy and ether-containing oxyalkylene esters for treating metabolic conditions |
US6030961A (en) * | 1997-03-11 | 2000-02-29 | Bar-Ilan Research & Development Co., Ltd. | Oxyalkylene phosphate compounds and uses thereof |
US6599937B1 (en) | 1997-03-11 | 2003-07-29 | Beacon Laboratories, Inc. | Unsaturated oxyalkylene esters and uses thereof |
US6316038B1 (en) | 1997-03-17 | 2001-11-13 | Btg International Limited | Therapeutic compositions |
US6323237B1 (en) | 1997-03-17 | 2001-11-27 | Btg International Limited | Therapeutic compositions |
US6207856B1 (en) | 1997-03-17 | 2001-03-27 | Btg International Limited | Therapeutic compositions |
EP2283834A3 (en) * | 1997-03-17 | 2012-02-01 | BTG International Limited | Therapeutic compositions comprising ketone bodies or their precursors |
AU749638B2 (en) * | 1997-03-17 | 2002-06-27 | Btg International Limited | Therapeutic compositions |
US8242172B2 (en) | 1998-02-11 | 2012-08-14 | Trustees Of Boston University | 2,2-dimethylbutyric acid oral pharmaceutical compositions |
US7485743B2 (en) | 2004-07-20 | 2009-02-03 | Btg International Limited | Oligomeric ketone compounds |
US11701363B2 (en) | 2009-09-24 | 2023-07-18 | Trustees Of Boston University | Methods for treating viral disorders |
US8993581B2 (en) | 2009-09-24 | 2015-03-31 | Trustees Of Boston University | Methods for treating viral disorders |
US8618068B2 (en) | 2009-12-08 | 2013-12-31 | Trustees Of Boston University | Methods and low dose regimens for treating red blood cell disorders |
US10857152B2 (en) | 2010-03-11 | 2020-12-08 | Trustees Of Boston University | Methods and compositions for treating viral or virally-induced conditions |
CN113194733A (en) * | 2018-12-18 | 2021-07-30 | 雀巢产品有限公司 | Mixed triglycerides |
WO2020127182A1 (en) * | 2018-12-18 | 2020-06-25 | Société des Produits Nestlé S.A. | Mixed triglyceriges |
US10953011B2 (en) | 2019-05-31 | 2021-03-23 | Viracta Therapeutics Inc. | Methods of treating virally associated cancers with histone deacetylase inhibitors |
Also Published As
Publication number | Publication date |
---|---|
GB8321595D0 (en) | 1983-09-14 |
AU1795383A (en) | 1984-02-16 |
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Legal Events
Date | Code | Title | Description |
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WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |