WO1999022725A1 - Procede de modification de la vitesse de croissance, de l'indice de consommation et de la composition corporelle des animaux domestiques - Google Patents
Procede de modification de la vitesse de croissance, de l'indice de consommation et de la composition corporelle des animaux domestiques Download PDFInfo
- Publication number
- WO1999022725A1 WO1999022725A1 PCT/US1998/023518 US9823518W WO9922725A1 WO 1999022725 A1 WO1999022725 A1 WO 1999022725A1 US 9823518 W US9823518 W US 9823518W WO 9922725 A1 WO9922725 A1 WO 9922725A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- dopa
- animal
- drug
- effective amount
- comprises administering
- Prior art date
Links
- 241001465754 Metazoa Species 0.000 title claims abstract description 101
- 238000000034 method Methods 0.000 title claims abstract description 49
- 239000000203 mixture Substances 0.000 title description 3
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims abstract description 105
- 210000003205 muscle Anatomy 0.000 claims abstract description 21
- 230000001965 increasing effect Effects 0.000 claims abstract description 17
- 150000004671 saturated fatty acids Chemical class 0.000 claims abstract description 17
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 16
- 235000021122 unsaturated fatty acids Nutrition 0.000 claims abstract description 15
- 150000004670 unsaturated fatty acids Chemical class 0.000 claims abstract description 15
- 235000003441 saturated fatty acids Nutrition 0.000 claims abstract description 9
- 229940079593 drug Drugs 0.000 claims description 36
- 239000003814 drug Substances 0.000 claims description 36
- 230000037396 body weight Effects 0.000 claims description 27
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims description 21
- 229960003151 mercaptamine Drugs 0.000 claims description 21
- 239000003112 inhibitor Substances 0.000 claims description 8
- 108010015720 Dopamine beta-Hydroxylase Proteins 0.000 claims description 6
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 6
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 6
- 239000000534 dopa decarboxylase inhibitor Substances 0.000 claims description 6
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 6
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 claims description 3
- 102100033156 Dopamine beta-hydroxylase Human genes 0.000 claims 5
- 230000003028 elevating effect Effects 0.000 abstract description 4
- 230000004075 alteration Effects 0.000 abstract description 3
- 150000001413 amino acids Chemical class 0.000 abstract description 3
- 230000003247 decreasing effect Effects 0.000 abstract description 2
- 230000000694 effects Effects 0.000 description 8
- 235000019625 fat content Nutrition 0.000 description 7
- 241000287828 Gallus gallus Species 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 4
- 235000013372 meat Nutrition 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 210000000579 abdominal fat Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000019197 fats Nutrition 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 235000019786 weight gain Nutrition 0.000 description 3
- DGMPVYSXXIOGJY-UHFFFAOYSA-N Fusaric acid Chemical compound CCCCC1=CC=C(C(O)=O)N=C1 DGMPVYSXXIOGJY-UHFFFAOYSA-N 0.000 description 2
- ZNXZGRMVNNHPCA-UHFFFAOYSA-N Pantetheine Natural products OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS ZNXZGRMVNNHPCA-UHFFFAOYSA-N 0.000 description 2
- DJWYOLJPSHDSAL-UHFFFAOYSA-N Pantethine Natural products OCC(C)(C)C(O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)C(O)C(C)(C)CO DJWYOLJPSHDSAL-UHFFFAOYSA-N 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- ZNXZGRMVNNHPCA-VIFPVBQESA-N pantetheine Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS ZNXZGRMVNNHPCA-VIFPVBQESA-N 0.000 description 2
- DJWYOLJPSHDSAL-ROUUACIJSA-N pantethine Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)CO DJWYOLJPSHDSAL-ROUUACIJSA-N 0.000 description 2
- 229960000903 pantethine Drugs 0.000 description 2
- 235000008975 pantethine Nutrition 0.000 description 2
- 239000011581 pantethine Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 235000021081 unsaturated fats Nutrition 0.000 description 2
- WGNUNYPERJMVRM-UHFFFAOYSA-N 3-pyridylacetic acid Chemical compound OC(=O)CC1=CC=CN=C1 WGNUNYPERJMVRM-UHFFFAOYSA-N 0.000 description 1
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- JDMUPRLRUUMCTL-VIFPVBQESA-N D-pantetheine 4'-phosphate Chemical compound OP(=O)(O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS JDMUPRLRUUMCTL-VIFPVBQESA-N 0.000 description 1
- 208000015580 Increased body weight Diseases 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- BNQDCRGUHNALGH-UHFFFAOYSA-N benserazide Chemical compound OCC(N)C(=O)NNCC1=CC=C(O)C(O)=C1O BNQDCRGUHNALGH-UHFFFAOYSA-N 0.000 description 1
- 229960000911 benserazide Drugs 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 229960004205 carbidopa Drugs 0.000 description 1
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- RZPNFYXFSHGGBE-UHFFFAOYSA-N cysteamine S-phosphate Chemical compound NCCSP(O)(O)=O RZPNFYXFSHGGBE-UHFFFAOYSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 1
- 229960002563 disulfiram Drugs 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 235000021083 high saturated fats Nutrition 0.000 description 1
- 229950007593 homonicotinic acid Drugs 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229940067619 phosphocysteamine Drugs 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 238000009394 selective breeding Methods 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
Definitions
- Another object of the present invention is to provide a method of reducing the saturated/unsaturated fatty acid ratio in the muscle tissue of domestic animals by administering an effective amount of L-DOPA, a drug that increases the amount of L-DOPA in an animal's bloodstream, or a combination thereof.
- Another object of the present invention is to provide a method for reducing total fat content of domestic animals by administering an effective amount of L-DOPA, a drug that increases the amount of L-DOPA in an animal's bloodstream, or a combination thereof.
- the method comprises elevating the level of the amino acid L-Dihydroxyphenylalanine (L-DOPA) in the bloodstream of the domestic animal by administering an effective amount of L-DOPA, a drug that increases the amount of L-DOPA in an animal's bloodstream, or a combination thereof, so as to achieve the desired alteration in body content, growth rate, feed efficiency, or any combination thereof.
- L-DOPA amino acid L-Dihydroxyphenylalanine
- L-DOPA amino acid L-Dihydroxyphenylalanine
- L-DOPA is intended to include molecules containing substitutions in the chemical formula of L-DOPA not affecting the chemical activity and efficacy of the L-DOPA molecule in this application.
- An effective amount is intended to mean a quantity of L- DOPA which, when administered to a domestic animal, will cause the muscle tissue of that animal to have a noticeable reduction of either the saturated fatty acid content, the ratio of saturated to unsaturated fatty acids, the total fat content of the animal, or an increase in feed efficiency. Reduction of the saturated fatty acid and fat contents and a reduction of the ratio of saturated to unsaturated fatty acids are significant benefits to the meat-consuming public. The increase in the feed efficiency provided by the methods of the present invention are of significant benefit to the producers of domestic animals, as greater amounts of meat can be obtained from such animals at less cost.
- feed efficiency is defined as the ratio of the weight of feed necessary to achieve one weight unit of body weight in a domestic animal. For example, using the weight unit “pounds”, a feed efficiency of 1 .8 would mean that it required 1 .8 pounds of feed in order to effect a 1 pound body weight gain in a domestic animal.
- An "adult” domestic animal refers to a domestic animal capable of breeding.
- the rates and amounts at which the L-DOPA can be administered to domestic animals to alter their body composition according to the methods of the invention may be varied. Additionally, one skilled in the art can vary the methods of administration to achieve optimum results.
- the preferred dosage of L-DOPA is from between about 40 and about 300 mg/kg of body weight per day, preferably from about 40 to 1 50 mg/kg of body weight per day.
- the invention lies in the discovery that elevating L-DOPA in the bloodstream of domestic animals has the effect of reducing fatty acid and fat content and saturated to unsaturated fat ratios in the muscle tissue of the domestic animals. Further, elevation of L-DOPA in the bloodstream of domestic animals increases the feed efficiency and growth rates of the animals.
- L-DOPA can be administered to domestic animals, other than by addition to feed. For example, one could administer conventional injections of the L-DOPA to the animals. One could also administer timed-release subcutaneous implants or injections of L-DOPA.
- L-DOPA in the Examples described herein was administered orally with animal feed, which is the preferred method of administration, the beneficial effects are believed to be derived from an elevated L-DOPA level in the bloodstream of the animals.
- drugs which inhibit the degradation of L-DOPA may also be administered and achieve the same effect.
- dopa decarboxylase inhibitors are carbidopa and benserazide, both of which have been used in conjunction with L-DOPA in the treatment of Parkinson's disease.
- These inhibitors may also be administered orally, in the food of domestic animals, or by implant or injection, as described above for L-DOPA.
- the amount of L-DOPA required to be administered can be reduced or eliminated resulting in a substantial economic savings.
- food containing naturally occurring L- DOPA or drugs which stimulate L-DOPA synthesis may be administered to the domestic animals.
- Drugs which stimulate L-DOPA synthesis include, but are not limited to, tyrosine, phenylalanine, and inhibitors of the enzyme dopamine beta hydroxylase such as fusaric acid, disulfiram, and cysteamine or pantethine and their derivatives.
- Such derivatives include, without limitation, phosphocysteamine, pantetheine, 3-pyridineacetic acid and 3-(3- pyridylmethoxycarbonyD-propionic acid esters of pantethine and pantetheine, and pantetheine-4'-phosphate.
- These agents can also be administered by conventional injection or by time-release subcutaneous implant or injection.
- Preferred dosages of such L-DOPA stimulating agents are from between about 50 and 500 mg/kg of body weight per day, preferably between about 1 00 and 200 mg/kg of body weight per day.
- the present invention is intended to include any method by which the level of L-DOPA in domestic animals may be artificially elevated in order to produce meat having a lower saturated fatty acid and fat level and a reduced ratio of saturated to unsaturated fatty acids. It is also intended to include any method by which the level of L-DOPA in domestic animals may be artificially elevated in order to increase the animal's growth rate or feed efficiency, relative to animals which are not being administered L-DOPA. Administration of combinations of L-DOPA and other drugs which elevate the level of L-DOPA in the bloodstream of domestic animals are also within the scope of the present invention.
- White Leghorn layer hens were fed standard layer diets supplemented with either L-DOPA (50 mg/kg body weight) or a combination of L-DOPA (50 mg/kg) and Cysteamine (230 mg/kg) for 7 weeks. At the end of the treatment period, 1 5 were sacrificed (5/group) and breast muscle samples obtained for fatty acid analysis.
- L-DOPA 50 mg/kg body weight
- Cysteamine 230 mg/kg
- Layer hens were treated at 48 weeks of age with either L-DOPA only (50 or 1 00 mg/kg body weight), cysteamine only (230 mg/kg body weight), or a combination of L-DOPA and cysteamine (50 mg/kg and 230 mg/kg respectively) for 7 weeks. Hens were sacrificed and abdominal fat dissected and weighed.
- a Denotes a value that is significantly different from control group (P ⁇ 0.05)
- ⁇ Denotes the average of all measurements ⁇ standard error * At this level of cysteamine, the animals stopped eating * * Female animals were sampled in this treatment group; abdominal fat data from females is omitted.
- the average body weight of all of the broilers which were given L-DOPA, cysteamine, or a combination were evaluated weekly until day 56.
- the average body weight for each treatment group at each measurement is shown in Table 4.
- L-DOPA at 1 00 mg/kg and L-DOPA at 1 00 mg/kg plus 1 00 mg/kg cysteamine increased the feed efficiency of the broiler chickens.
- L-DOPA 50, 1 00, and 200 mg/kg body weight
- L-DOPA + cysteamine L-DOPA 50 mg/kg + cysteamine 230 or 400 mg/kg
- cysteamine only 230 mg/kg or 400 mg/kg
- the above described studies and method of the invention were done on poultry, one kind of domestic animal.
- the current invention is applicable to all domestic animals which produce meat for consumption by humans.
- the method could be used to reduce the fat content and saturated/unsaturated fatty acid ratio in the muscle tissue of beef cattle or swine, or to increase the growth rate and/or feed efficiency of such animals prior to slaughter.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
La présente invention concerne un procédé permettant de réduire la quantité d'acides gras saturés, de réduire le rapport entre les acides gras saturés et les acides gras insaturés dans les tissus musculaires, de diminuer la quantité de graisse totale, et d'accroître la vitesse de croissance et l'indice de consommation chez les animaux domestiques. Ce procédé consiste à augmenter le niveau de l'acide aminé L-Dihydroxyphénylalanine (L-DOPA) dans la circulation sanguine de l'animal domestique, de manière à réaliser les modifications désirées dans la composition corporelle et/ou dans l'indice de consommation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU13813/99A AU1381399A (en) | 1997-10-31 | 1998-10-30 | Method for modifying the growth rate, feed efficiency and body composition of domestic animals |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6393097P | 1997-10-31 | 1997-10-31 | |
| US60/063,930 | 1997-10-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1999022725A1 true WO1999022725A1 (fr) | 1999-05-14 |
Family
ID=22052431
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1998/023518 WO1999022725A1 (fr) | 1997-10-31 | 1998-10-30 | Procede de modification de la vitesse de croissance, de l'indice de consommation et de la composition corporelle des animaux domestiques |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU1381399A (fr) |
| WO (1) | WO1999022725A1 (fr) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4711897A (en) * | 1985-04-24 | 1987-12-08 | Smithkline Beckman Corporation | Animal feed methods and compositions using cysteamine |
| US5665375A (en) * | 1995-05-31 | 1997-09-09 | Board Of Supervisors Of Louisiana University And Agricultural And Mechanical College | Method of altering the contents of eggs |
-
1998
- 1998-10-30 AU AU13813/99A patent/AU1381399A/en not_active Abandoned
- 1998-10-30 WO PCT/US1998/023518 patent/WO1999022725A1/fr active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4711897A (en) * | 1985-04-24 | 1987-12-08 | Smithkline Beckman Corporation | Animal feed methods and compositions using cysteamine |
| US5665375A (en) * | 1995-05-31 | 1997-09-09 | Board Of Supervisors Of Louisiana University And Agricultural And Mechanical College | Method of altering the contents of eggs |
Non-Patent Citations (4)
| Title |
|---|
| CHEMICAL ABSTRACTS, 1 January 1900, Columbus, Ohio, US; abstract no. 122:313533, XP002916177 * |
| CHEMICAL ABSTRACTS, 1 January 1900, Columbus, Ohio, US; abstract no. 84:120174, XP002916174 * |
| DATABASE WPI 1 January 1900 Derwent World Patents Index; AN 84-01071, XP002916175, GREIF Z, ET AL: "Growth Enhancement Induced by Prolonged L-Dopa Administration in Rats" * |
| DATABASE WPI 1 January 1900 Derwent World Patents Index; AN 90-08478, XP002916176, LANES R, ET AL: "Effect of Chronic L-Dopa Administration on Linear Growth and GH Secretion in Healthy Prepubertal Short Children" * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU1381399A (en) | 1999-05-24 |
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