Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution...
Reexamination Certificate
2002-06-17
2004-10-26
Tate, Christopher R. (Department: 1654)
Drug, bio-affecting and body treating compositions
Plant material or plant extract of undetermined constitution...
C536S005000
Reexamination Certificate
active
06808723
ABSTRACT:
This invention relates to the reduction of gastric acid secretion in animals including humans; to methods of treating conditions or disorders associated with or exacerbated by gastric acid secretion; to pharmaceutical compositions useful in carrying out such methods; and to the use of certain extracts and compounds in the treatment of human and non-human animals, generally mammals.
Excessive secretion of gastric acid can lead to or aggravate a number of disorders, for example oesophageal reflux disease, e.g. reflux oesaphagitis, haemorrhage in and benign ulceration of the stomach and duodenum (including those complicating NSAID therapy). These conditions tend to be more problematical in obese patients and patients with hiatus hernia. The present invention is directed, in part, to the treatment of these conditions and of ancillary indications, e.g. to provide relief of reflux-like symptoms (e.g. heartburn) and/or ulcer-like symptoms (e.g. epigastric pain) associated with acid-related dyspepsia; for general dyspeptic symptoms; and for prophylaxis of acid aspiration.
Non-steroidal anti-inflammatory drugs (NSAIDs), e.g. aspirin (acetylsalicylic acid), are well-known and widely used for their anti-inflammatory and antipyretic properties. A major side effect is their tendency to damage the wall of the stomach; this adverse property is acid-dependent and is generic to the NSAIDs. The present invention is also concerned with means for mitigating these adverse effects.
It is known from International Patent Publication No. WO 98/46243 that extracts of certain plants of the genus
Trichocaulon
or
Hoodia
possess appetite suppressant properties. This document also discloses certain specific compounds which possess appetite suppressant activity. Among these is the compound 3-O-[-&bgr;-D-thevetopyranosyl-(1→4)-&bgr;-D-cymaropyranosyl-(1→4)-&bgr;-D-cymaropyranosyl]-12&bgr;-O-tigloyloxy-14-hydroxy-14&bgr;-pregn-5-en-20-one; the structural formula of this compound is given as formula (1) in WO 98/46243. We have found that this compound is effective in reducing the secretion of gastric acid; accordingly, the compound finds application in the present invention. Derivatives of this compound are also effective in the present invention; such derivatives have the general formula
in which R=alkyl;
R
1
=H, alkyl, tigloyl, benzoyl, or any other organic ester group;
R
2
=H, or one or more 6-deoxy carbohydrate, or one or more 2,6-dideoxy carbohydrates, or glucose molecules, or combinations thereof;
in which the acyl group R—(C═O)— group can be in the reduced form R—(C—OH)—;
and in which the dashed lines indicate the optional presence of a double bond in the C4-C5 or C5-C6 positions.
Thus, according to a first aspect of the present invention, there is provided a method of reducing gastric acid secretion in an animal, which comprises administering to said animal:
(a) an extract of a plant of the genus
Hoodia
or
Trichocaulon
; or
(b) a compound of the formula
wherein: R=an alkyl group containing from one to four carbon atoms;
R
1
=H, an alkyl group containing from one to four carbon atoms, or an organic ester group;
R
2
=H, or one or more 6-deoxy carbohydrates, or one or more 2,6-dideoxy carbohydrates, or glucose, or a combination thereof;
and in which the dashed bonds indicate the optional presence of a double bond at the C4-C5 position or the C5-C6 position.
Advantageously, when R
1
is an organic ester group it is tigloyl, benzoyl or anthraniloyl. In a preferred embodiment, R is an alkyl group having from one to four carbon atoms, R
1
is tigloyl or anthraniloyl; and a double bond is present in the C5-C6 position.
Advantageously, R
2
is trisaccharide group. The component sugars of said trisaccharide group are preferably 6-deoxy and/or 2,6-dideoxy hexoses. In some embodiments, the terminal hexose moiety is thevetosyl.
The compound may be 3-O-[-&bgr;-D-thevetopyranosyl-(1→4)-&bgr;-D-cymaropyranosyl-(1→4)-&bgr;-D-cymaropyranosyl]-12&bgr;-O-tigloyloxy-14-hydroxy-14&bgr;-pregn-5-en-20-one.
According to a second aspect of the present invention, there is provided a method of treating a disorder of the alimentary system in an animal, which comprises administering to the animal
(a) an extract of a plant of the genus
Hoodia
or
Trichocaulon
; or
(b) a compound of the formula
wherein: R=an alkyl group containing from one to four carbon atoms;
R
1
=H, an alkyl group containing from one to four carbon atoms, or an organic ester group;
R
2
=H, or one or more 6-deoxy carbohydrates, or one or more 2,6-dideoxy carbohydrates, or glucose, or a combination thereof;
and in which the dashed bonds indicate the optional presence of a double bond at the C4-C5 position or the C5-C6 position.
This method can conveniently be used in the treatment of reflux oesophagitis. It is also expected to find application in the treatment of epigastric pain; dyspepsia; gastric ulceration; and acid aspiration.
According to a third aspect of the present invention, there is provided a method of protecting a mammalian gastrointestinal tract from damage caused by a non-steroidal anti-inflammatory drug, which comprises administering an effective amount of:
(a) an extract of a plant of the genus
Hoodia
or
Trichocaulon
; or
(b) a compound of the formula
wherein: R=an alkyl group containing from one to four carbon atoms;
R
1
=H, an alkyl group containing from one to four carbon atoms, or an organic ester group;
R
2
=H, or one or more 6-deoxy carbohydrates, or one or more 2,6-dideoxy carbohydrates, or glucose, or a combination thereof;
and in which the dashed bonds indicate the optional presence of a double bond at the C4-C5 position or the C5-C6 position.
According to a fourth aspect, the present invention provides a method of protecting a mammalian gastro-intestinal tract from damage caused by a non-steroidal anti-inflammatory drug, which comprises administering an effective amount of |3-O-[-&bgr;-D-thevetopyranosyl-(1→4)-&bgr;-D-cymaropyranosyl-(1→4)-&bgr;-D-cymaropyranosyl]-12&bgr;-O-tigloyloxy-14-hydroxy-14&bgr;-pregn-5-en-20-one or a derivative thereof.
When a plant extract is used in the invention, it is presently preferred to use an extract from the plant
Hoodia gordonii
or
Hoodia currori
. Advantageously, the said extract comprises spray-dried sap of the plant
Hoodia gordonii.
The methods in accordance with this invention are applicable to the treatment of humans.
According to a fifth aspect of the present invention, there is provided a pharmaceutical composition comprising a non-steroidal anti-inflammatory drug and a compound of the formula
wherein: R=an alkyl group containing from one to four carbon atoms;
R
1
=H, an alkyl group containing from one to four carbon atoms, or an organic ester group;
R
2
=H, or one or more 6-deoxy carbohydrates, or one or more 2,6-dideoxy carbohydrates, or glucose, or a combination thereof;
in which the acyl group R—(C═O)— group can be in the reduced form R—(C—OH)—;
and in which the dashed bonds indicate the optional presence of a double bond at the C4-C5 position or the C5-C6 position.
A preferred pharmaceutical composition of this type utilises the compound 3-O-[-&bgr;-D-thevetopyranosyl-(1→4)-&bgr;-D-cymaropyranosyl-(1→4)-&bgr;-D-cymaropyranosyl]-12&bgr;-tigloyloxy-14-hydroxy-14&bgr;-pregn-5-en-20-one or a derivative thereof. The pharmaceutical compositions of this invention are conveniently prepared in unit dosage form; they may also include a pharmaceutically acceptable diluent, excipient or carrier.
According to a sixth aspect of the present invention, there is provided method of treating a condition or disorder caused by or exacerbated by gastric acid secretion in an animal, which comprises administering to the animal a pharmaceutical composition as just defined. The animal may be a human.
According to a seventh aspect, the present invention provides the use of a compound of the formula
Hakkinen John
Horak Roelof Marthinus
Maharaj Vinesh
Flood Michele
Morgan & Lewis & Bockius, LLP
Phytopharm PLC
Tate Christopher R.
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