JPH01258622A - Method and composition for controlling ratio of protein and fat of animal - Google Patents

Abstract

PURPOSE: To adjust a protein to fat ratio by parenterally administering cobalt protoporphyrin(CoPP) or cobalt mesoporphyrin(CoMP) for suppressing the endocrine system of an animal. CONSTITUTION: This method for increasing a protein to fat ratio in an animal, is to administer an effective amount for a suppression, preferably 1-50μmol/Kg body weight CoPP or CoMP as an aseptic parenteral isotonic solution intravenously, subcutaneously or intramuscularly for increasing the protein ratio against the body weight. In breeding a beef cattle or a domestic fowl for a food, a feed efficiency is improved and a lean meat having a high nutritious value can be obtained. By administering CoPP or CoMP, the production of gonadal hormones is temporarily suppressed with an accompanying reduction of anabo1ic and growth accelerating activities, and also an appetite adjusting site in a hypothalamus is affected to obtain an appetite suppression for a long period of time.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a method for inhibiting the endocrine system of animals. More specifically, the present invention relates to cobalt protoporphyrin (
CoPP ) or cobalt mesoporphyrin (CoPJ
P) By treatment with IIC, the animals, i.e. cattle;
In particular beef cattle; sheep; goats; poultry, especially chickens, mammals such as ducks and turkeys, and fish, especially fish kept in fish farms such as salmon and trout; and all animals of economic importance, including animals and even bettas. It relates to methods of limiting the activity of endocrine glands to achieve desired physiological results, such as suppression of hormone production. The present invention also provides CoP
The present invention relates to therapeutically useful isotonic compositions containing P and/or CoF, (P). Both of these compounds are known.

PRIOR TECHNOLOGY, PROBLEMS TO BE SOLVED BY THE INVENTION The endocrine system is concerned with phenotype, homeostasis, size and individual lines, as well as body weight coefficients such as body weight and protein-to-fat ratio (P/F). It is a thread involved in the production and distribution of hormones in animals. The main organs of the endocrine system are the hypothalamus, pituitary gland (anterior and posterior lobes), parathyroid glands, thyroid, thymus, adrenal glands, pancreas, and gonads (male testes and female ovaries). The organs of this system secrete one or more hormones that help regulate the visceral functions of target organs. For example, ADH (antidiuretic hormone) called vasopressin is secreted by the posterior pituitary gland and promotes water reabsorption by the kidneys. This is thought to be regulated by the hypothalamus.

The lower part of the body is believed to regulate the secretion of antidiuretic hormone ADH. When certain cells in the lower part of the bed sense that there is a lack of water in the blood, the nerve fibers in the hypothalamus secrete it by the posterior pituitary gland.
is released. ADH moves to its target L3 site in the bloodstream, the kidneys. - and helps the kidneys reabsorb water so that the blood becomes more diluted. When the number of facets becomes diluted due to reabsorbed water, this fact is sensed in the hypothalamus and the production of *A D i (stops).

In some cases, the target organ of one endocrine gland is another gland of the same system. For example, is the trophic hormone in the anterior pituitary gland, such as luteinizing hormone (L) (), a gonadal gland? Stimulate test tetron, varnish! Produces androgens such as rogens and hyprogesterone.

Growth hormone (GH) produced in the anterior pituitary gland determines the size of an individual, and therefore has a great influence on the phenotype of mammals. This hormone causes protein accumulation in almost every cell in the body.

All tissues, including bone, grow in response to GH. As long as some cartilage remains at each end, bones continue to grow throughout the child's life. Growth stops when this area of cartilage turns into bone. The long tube completes its growth at the same time as adulthood.

The amount of GH produced during early puberty determines the size of an individual. If the amount produced is too small or not present at all, the person becomes a dwarf. If too much GHQ is generated, it becomes a giant.

When GH production increases in adulthood, only the bones of the jaw, eyebrows, nose, fingers and toes can respond. When these begin to grow, they appear abnormal with very large fingers and toes. This is one result of pituitary hyperfunction. This is diagnosed as acromegaly. It is thought that Goliath, who appears in the book, had this acromegaly.

Other such conditions are also known.

It is useful to suppress the production of undesirable hormones when there is an excess production of the hormone or an undesirable response to the normal production of hormones that results in undesirable weight gain or increased growth rate. This method was discovered.

It has been discovered that by treatment with specific metalloporphyrins it is possible to suppress the internal mA in mammals, which is associated with overactivity of one or more glands of the endocrine system. It became possible to cure the suffering of the human race.More specifically, Co.
When PP was administered to mammals, heme oxygenase activity was strongly stimulated, and at the same time suppression of ALA synthetase activity and significant suppression of the endocrine system were observed.

Means for Solving the Problems A particularly important aspect of the present invention is that CoPP and CoMP have the ability to limit the production of gonadal male and female hormones, such as testotetron and estrogen, and the ability to limit the production of thyroid hormones. It is to have.

Gonadal hormones have anaporic activity. These hormones and their synthetic analogs are used to promote growth.

Too much production of anaporic hormones increases growth rate with increased food intake. CoPP or CoM
One of the rapid effects of administering P to animals is a rapid decrease in appetite and a consequent decrease in growth rate. The above effects continue as long as the concentration of gonadal hormones is lower than that of the untreated mammal. Surprisingly, this reduction in growth rate persists even after gonadal levels return to normal. As explained below, in rats, the low levels of testosterone last for about 48 days, but the reduced growth rate lasts for at least 90 to 100 days. The animal appears normal except for an increased P/F ratio. The period of low testosterone levels can be controlled to a specific period by selecting the dose of CoPI' or CoMP.

The reduced growth rate seen in animals is further explained by CoPP or Co
The administration of MP may typically be maintained for more than 90 days, or for other selected periods of time, by administering at low dosage levels. In this way, C
oPP or CoMP can be used in animals to achieve and maintain a reduction in growth rate to help control body weight. 9 later! P/ in the body of @things treated with any of these metal salts as detailed in .
The F ratio increases somewhat.

As described below, when C0PP is administered to rats,
Plasma levels of the thyroid hormones T and T4 are traditionally reduced, and the pituitary-induced trophic hormone T81 (also reduced to lower than expected levels). Gonadal hormones such as these are lost from the plasma, and at the same time, the pituitary-induced trophic hormone LH also falls below normal levels.In addition, suppression of cortisol in the hypothalamus-pituitary-M11 renal axis VC8 and plasma cells was also observed. .

These findings indicate that terminal syncrine systems such as the thyroid, gonads, and adrenal glands are suppressed and that the consequences are associated with inhibition of pituitary hormone synthesis or release. When the pituitary gland is examined under a microscope, thyroid-releasing cells (T S
) is found to be <4 pears smaller in CoPP-treated animals than in normal versus l·:1 animals.

EXAMPLES The accompanying drawings show the results of studies carried out on rats and clearly illustrate the effect of CoPP on suppressing the activity of the endocrine system. Similar results are obtained for CoMP.

Figures 1A and 1B are graphical representations of the experimental results, showing that CoPP suppresses the endocrine system of rats. Specifically, in this example, aspects of the endocrine system, including the pituitary-testis axis, are shown to be suppressed. Panel A of Figure 1 shows serum testosterone levels in rats given two doses of CoPP, with hormone measurements taken 7 days after the first injection. As seen in the control section on the left, serum testosterone levels prior to C0PP administration were within the expected range for this type of animal. In the data shown on the right side of this panel (labeled CoPP), the serum testosterone levels after CoPP administration were all below 0.8 nV-, which is an abnormally low serum level of this male sex hormone. In panel B on the right, serum LH levels, which control the synthesis and release of testosterone from the gonads and are themselves produced and released from the pituitary gland under hypothalamic stimulation, are shown. The control group represents the range of normal levels of serum LH administered to this type of animal. The CoPP data on the right side of this panel shows that despite the large decrease in serum testosterone levels shown in the left panel of this figure, there was no compensatory increase in the release of serum LH from the pituitary as would normally be expected. ing.

In these studies the CoPP dose level was 50
It was μmol/ky (body weight). The number of animals is indicated by the number of dots.

It is known that there is a feedback regulatory endocrine mechanism in which the terminal and central endocrine glands, in this case the pituitary-gonadal axis, act to maintain hormone levels at a suitable constant equilibrium level. That is, if serum testosterone levels decrease significantly, serum LH levels should rapidly increase to return serum testosterone levels to normal levels. Contrary to the expected increase, CoP
Do animals treated with P show any such compensatory increase? Didn't show it. This is clear from FIG. 1B. This suggests that the compensatory mechanisms for stimulating increases in serum testosterone were impaired by CoPP, and for reasons that are not clear, the LH required to correct the imbalance in the production of testosterone produced by COPP was impaired. This indicates that the pituitary gland was unable to release. That is,
Decreased serum testosterone levels in these animals will reduce serum LH levels which will return serum sex hormone levels to normal.
was not compensated for by the repulsive increase in

This indicates a significant decline in endocrine function at the central and terminal levels. Synthetic metalloporphyrins act at higher levels than the endocrine glands, specifically at a point in the pituitary-hypothalamus axis from which releasing hormones (e.g., LH-releasing hormone) are directed to the pituitary gland. sent,
It is clearly shown here that the release of trophic hormones (in this case L) () is stimulated.

Similar results can be obtained with CoMP.

Figure 2 shows CoPP at 2 s μmol/ky (body weight)
It has been shown that the suppressive effect on serum testosterone levels is sustained by administration of -2 times. That is, the salary graph shows that serum testosterone levels are at significantly lower than normal levels from day 14 to 40, consistent with the data in Figure 1. Hormone levels gradually return to normal levels, but do not fall within the normal range until 48 days have passed. A single administration of CoPP can significantly suppress the synthesis and release of gonadal sex hormones and growth hormones, such as testosterone, and the synthesis or release of nutritional hormones for gonadal hormone production (LH). This effect was shown to be 40-4 after a single injection of any of the metalloporphyrins of the invention.
It can last for 8 days. This ability to temporarily suppress important endocrine systems, such as the hypothalamic-pituitary monogonadal axis, is a novel biological effect achieved by administering the metalloporphyrins described herein, and is a novel biological effect achieved by administering the metalloporphyrins described herein. This clearly demonstrates the usefulness of these substances in the treatment of diseases caused by levels. In other studies, the 48-day inhibition mentioned above was due to CoPP.
9 by repeated administration at periodic intervals.
It was extended for several months.

This clearly shows that periodic administration of the synthetic metalloporphyrins of the present invention provides a useful means for suppressing endocrine function for as long as the administration continues.

In Figure 2, the number above each bar graph is the number of test animals. Horizontal dotted lines indicate the range of testosterone levels in control animals.

The inhibition of gonadal and thyroid hormone production in endocrine threads by CoPP and CoMP is reversible.

- When administration of the modified compound is discontinued, the normal internal fraction (B, 1%
gradually and completely recover. This administration of compounds is of great value in clinical settings, where it is not known to what extent physical complaints are due to excessive levels of certain endocrine substances. This can be determined by the successful use of appropriate doses of CoPP or COMF to suppress endocrine function, restoring normal levels when the effects of this compound have diminished. However, although the endocrine threads return to their normal state by normal means, the growth rate remains depressed for many weeks.

Figure gg3 shows comparative data for the pituitary-thyroid axis. Panel Human Serum T4 (Thyroxine) in Animals
Indicates the level and its normal range. In this panel, the column labeled CoPP indicates that animals were treated with CoPP using the same method as in the study on the sex hormone testosterone.
Panel B shows a similar decrease in the levels of another major thyroid hormone, T, by treatment with 2-50 ttsnoJl/kg (body weight). Its plasma levels in animals and the lowering effect on plasma levels of this hormone brought about by CoPP are shown.Finally, panel C shows the trophic hormone for the thyroid gland, namely thyroid stimulating hormone (T8), in control and CoPP-treated animals.
Serum levels of H) are shown. In animals, including humans, when thyroid levels are significantly reduced (K as shown in the previous two panels of the figure), blood WJTSH levels return to significantly higher levels than seen in control conditions. However, panel C
As shown, there was no such relapse in animals treated with CoPP. This indicates that the pituitary gland in these animals was unable to respond normally to the reduction in plasma levels of thyroid hormones (T4 and T,) caused by CoPP.

Similar results can be obtained using CoMP.

These findings, together with the findings in Figures 1 and 2 regarding the pituitary-gonadal origin, clearly demonstrate the hypothalamic effects of the synthetic metalloporphyrins of the present invention. This effect may be moderated by the action of these compounds on the releasing hormones for trophic hormones (LH or T8H) that control the terminal synthesis and secretion of thyroid and gonadal hormones or by other as yet unknown mechanisms. . That is, in these two endocrine axes, the synthetic metalloporphyrins CoPP and CoMP exhibit large suppressive effects even when administered in relatively small doses.

CoP from the results of these studies involving the pituitary-thyroid axis
It is clear that administration of P is effective in treating diseases in mammals associated with hyperthyroidism.

Figure 4 is a male (1) Sprague -Dawl ey
Figure 2 shows weight loss after administering a single dose of CoPP to rats (140-1609).

The parenteral solutions used in this study and others reported here contain CoPP or CoMP in small volumes of 0, 1 M
NaOH (0 per tnt of metalloporphyrin solution,
1 #! /). CoPP and CoMP were purchased from Volfhilling Products (Logan, UT). The pH of the solution is IM
Adjust to 7.4 with MCI, final volume is 0.9% NaC
It was prepared by adding K.1 solution. Administration was by subcutaneous injection.

In this study, rats were treated with the following CnPP solution on the first day.

50 μmol/kl (body weight) A 2 s ttmol/D (body weight) Bs μmol/
kt (body weight) C Saline D Each point on the figure represents the average body weight of 6 animals.

After an initial cessation or reduction in growth rate, 5-25 μmat/
kg-treated rats gained weight parallel to that of saline-treated controls, but their body weights were smaller than those of the controls. Rats treated with 50 μmol/ky rapidly lost weight and did not return to their initial weight even after 14 days. However, after day 14, the animals began to gain weight at a similar rate to the control animals.

Figure 5 shows the relationship between testosterone concentration and weight loss. Lower panel shows saline, A or Co PP at 25%
Daily overweight SEM of 6 rats treated with μg/ky (body weight) is shown. Blood was collected from the tail at the time points indicated in the figure.
Serum testosterone concentrations were determined as ffi (top panel). The upper SEM of 6 rats) B is shown in the upper panel.

In this study, testosterone levels decreased by approximately 90% within 4 days. Weight gain was constant for the last 4 days, decreased slightly in the following week, recovered in the following week, and increased to 20
The temperature increased from day to day 48 in parallel to that of the control. Untreated animals steadily gained weight throughout the study period. Serum testosterone levels were at very low levels within a period of 4 to 25 days. After that, it gradually recovered to the normal level and reached the normal level after 40 to 48 days of fishing.

Despite the fact that treated animals gained weight at a similar rate to control animals, their total body weight remained approximately 5% less than that of untreated animals, even when their serum testosterone levels normalized. there were. This condition continued for 90 to 100 days. Similar results were found in female rats by examining the relationship between estrogen levels and weight gain.

Another M''2 effect obtained by administering C0PP or CoMP is a significant increase in the P/F ratio of treated animals.

In one experiment illustrating this routine and essential result, 40 child Sprague-Daw
ley rats (160-2009) were divided into 5 groups of σNfiJ. One group received physiological saline and served as a control group. 10 μmol/kjI (body weight) of CoPP was parenterally administered to 32 deceased animals and observed for 180 days. Of these, 84 were not subjected to any further treatment. On the 11th day of the second week, the remaining 24
The animals were given another dose of CoPP f at the same dose. This treatment was repeated at two week intervals using 16 and 8 mice from the first group in succession. i.e., 10, 20, 30 and 40, respectively, in addition to the control group.
There were four groups that received amol/kt (body weight) of CoPP.

On day 180, the remaining animals were sacrificed and the total fat and protein in their bodies were measured. The results are shown in the table below.

Table 1 vs. i: () Physiological saline 19.6 19
．． 6 LOO/1.01 (0)PI' 1XIO
μmol/kj' (body: ]) 16.6 20.7
1.25/1.02 (OoPI' 2X10μm
ol/ni! , (Weight) 14.5 20.4 1.
41/1.03 (CbPP3 cut Opmol/kt compliance)
13.3 21.6 1. fi2/1.04
(CoPP 4X10μmOL/kP (weight) 11
4 21.4 1.73/1.0 A constant decrease in fat content was observed with increasing CoPP dosage. maximum C
The primary weight loss at the oPP dose is 41%. This decrease in fat content occurs without a statistical increase in protein 1, so that the P/F ratio is primarily 1.0.
/ 1.0 to 1.7-3 / 1. OK increased.

A single administration of this particular metalloporphyrin produces a similar effect as a series of treatments.

Those skilled in the art of animal agriculture will appreciate the economic significance of this aspect of the invention. In this way, it is possible to produce economically important animals, such as beef cattle and poultry, with a low fat content and a proportionately increased protein content. This is very important in animal agriculture for many reasons. The first is that feed efficiency will improve. Normally, it takes more feed to produce one bond of fat than to produce one bond of protein, and therefore costs more. Animals treated according to the invention have a lower fat content and therefore a higher protein to body weight ratio than untreated animals.

The edible tissues of treated animals are more nutritious than those of treated animals.

The second important result is that meat from treated animals has a lower fat content than its unprocessed counterpart.

Recent research has shown that high-protein, or lean, meat is better for human health than high-fat meat. It has long been recognized that fish caught in freshwater rivers and lakes or in saltwater taste better than those raised in fish farms.

This is because the latter type of fish has a high fat content. Therefore, the present invention will have a significant impact on this industry.

Duck meat is not the same as chicken or turkey meat. This is because duck meat has a high fat content. CoP
The use of P or CoMP will increase the popularity of duck as a food.

The following effects appear to be obtained by administering CoPP or CoMP to animals.

1, 7 A temporary decrease in the production of gonadal hormones with a concomitant decrease in growth-promoting activity.

2. Long-term appetite suppressing effects can be obtained by these compounds acting on the appetite regulating site in the hypothalamus.

3. Increase in P/F ratio.

It should be noted that endocrine studies in animals serve as a valid and academically accepted model of the regulatory mechanisms by which the human endocrine control system functions. That is, for example, the role of androgenic hormones in prostatic hyperplasia and the effect of castration (removal of the male sex hormone testotetron by removing the testicles) in reducing prostatic hypertrophy symptoms.
ugglns studied dogs. Similarly, elucidation of the major regulatory mechanisms for thyroid hormones was performed in rats and other animals. It has been established that the results should be similar in humans, allowing us to accurately predict the therapeutic effects that should be achieved by administering to humans drugs tested on animals. . That is, the consequences of endocrine suppression by CoPP in these animals have good relevance to the situation in humans;
This clearly shows that at certain doses the synthetic metalloporphyrin CoPP or CoMP will suppress the endocrine system in humans and other animals.

The endocrine system of the mammals described and exemplified here is significantly
This new-found ability to temporarily suppress the effects of cancer is of great clinical importance. This is because it may not be known to what extent a condition, such as an abnormally developed prostate or thyroid gland, is due to hormones. In the past, this led doctors to perform excisional surgery (
Castration, thyroidectomy, hypophysectomy, etc.) had to be performed. As a result of this discovery, it is now possible to administer small doses of CoPP and determine its suppressive effect on the symptoms in question (by suppressing the endocrine system and selectively replacing hormones that are not thought to be causative). It's very simple. Once such information is obtained, treatment can be continued by using specific metalloporphyrins to maintain suppression of the endocrine system, or, if certain, the appropriate endocrine glands can be surgically replaced.

This particular compound of the invention is typically administered parenterally, ie, intravenously, subcutaneously or intramuscularly, as a sterile parenteral isotonic solution. Any pharmaceutically acceptable diluent currently used in the preparation of parenteral compositions may be used in preparing such solutions. The solution is adjusted to a pH of about 7-8, preferably 7.4-7.5, e.g. by phosphate buffer.
It may be subjected to KM reaction, and may also contain salt or glucose as a solute. The solution may also contain polyhydric alcohols such as ethylene or propylene glyfur. The active compounds may also be administered as a solution or suspension in a sterile inert oil, such as sesame oil or peanut oil at °C. Typical dosing regimen is 1-50μ
The dosage would be divided into two doses per week, with a total dosage of y (body N) per mol/week. Your doctor or veterinarian will determine your specific dosage. The dosage will then depend on the condition being treated, the age, weight and state of health of the patient.

Typically, a predetermined amount of CoPP or CoMP is 0.1 M
Dissolved in sodium hydroxide aqueous solution and adjusted to the specified p in IM Salt City.
An isotonic solution can be prepared by adjusting the solution to H and forming a gold cap with a 0.9 aqueous sodium chloride solution. The concentration of active ingredient in parenteral compositions can be about 1 to 25 my/min.

Administration of the active ingredient suppresses the entire endocrine system, but is of particular value in limiting the production of gonadal and thyroid hormones and in controlling body weight and increasing the P/F ratio. Therefore, as indicated above, if an active ingredient is administered to suppress one endocrine function, such as the secretion of thyroid hormones, it may be necessary to simultaneously suppress the secretion of other adjunctive hormones (many of which are commercially available). processing may also compensate for the suppression of other endocrine functions.

This inhibitory effect of CoPP and CoMP diminishes over time and returns to normal except for growth rate, final body weight and P/F ratio. This occurs for a period that depends on the administration tK of the metalloporphyrin. That is, treatment can be continued for a specific period of time to cure or alleviate certain symptoms. Treatment may be discontinued after the first course or may be administered at different levels and for different periods of time.

Inorganic cobal), iron 7” rotovolphyrin (heme), tin glotovolphyrin and other metal porphyrins are CO
It does not have the effects of I'P and CoMP.

The requirement for endocrine suppression is that metalloporphyrins can stimulate heme oxygenase activity for long periods of time, 5 to 15 times longer in the hepatic thighs and possibly in the pituitary gland and hypothalamus, and in one direction. It would be possible to inhibit ALA-synthetase and cytochrome P-450 activity in these organs. These enzymes are the rate-limiting enzymes for heme degradation and heme synthesis, respectively. These enzymes may be included in the mechanism by which the active compounds of the invention inhibit the endocrine system.

[Brief explanation of the drawing]

The first flAEc and B are respectively Co
FIG. 2 is a graph showing the serum testosterone level and the serum LH level released from the pituitary gland of rats administered two doses of PP, and FIG. 2 is a graph showing the relationship between dish serum testosterone level and number of days according to the present example. and FIG. 3A, B, and C are CoPP lj according to this embodiment, respectively.
Serum T4 level, serum T, level and T S by 4 sciences
FIG. 4 is a graph showing the relationship between body weight and number of days after administration of one dose of CoPP to rats according to this example, and FIG. 5 is a graph showing the relationship between testosterone concentration and number of days according to this example. It is a graph showing body weight in relation to the number of days. Agent Masao Miyake and 1 other person○ 14 25 40 48 Salary (9) d3r: JIB) FIG. 5 -r- system sales IN 11 J (good 1 shot) March 1986
J] 2'7/II

Claims (1)

[Scope of Claims] 1. A method for suppressing gonadal hormone production in an animal, if necessary, which comprises parenterally administering an effective suppressive amount of cobalt protoporphyrin or cobalt mesoporphyrin. 2. The method according to claim 1, which comprises administering cobalt protoporphyrin. 3. The method of claim 1, which comprises administering cobalt mesoporphyrin. 4. The method according to claim 2, wherein the hormone is an androgenic hormone. 5. The method according to claim 2, wherein the hormone is an estrogen hormone. 6. The method according to claim 3, wherein the hormone is an androgenic hormone. 7. The method of claim 3, wherein the hormone is an estrogen hormone. 8. The dose of cobalt protoporphyrin is 1 to 50
The method according to claim 4, wherein the amount is μmol/kg (body weight). 9. The dose of cobalt protoporphyrin is 1 to 50
The method according to claim 5, wherein the amount is μmol/kg (body weight). 10. The dosage of cobalt mesoporphyrin is 1 to 50.
The method according to claim 6, wherein the amount is μmol/kg (body weight). 11. The dosage of cobalt mesoporphyrin is 1 to 50
The method according to claim 7, wherein the amount is μmol/kg (body weight). 12. A method for suppressing thyroid hormone production in an animal, if necessary, which comprises parenterally administering an inhibitory effective amount of cobalt protoporphyrin or cobalt mesoporphyrin. 13. The method of claim 12, which comprises administering cobalt protoporphyrin. 14. The method of claim 12, which comprises administering cobalt mesoporphyrin. 15. The method of claim 13, wherein the hormone is T_3. 16. The method of claim 13, wherein the hormone is T_4. 17. The dose of cobalt protoporphyrin is 1 to 5.
Claim 15 which is 0 μmol/kg (body weight)
Section method. 18. The dosage of cobalt protoporphyrin is 1 to 5.
Claim 16 which is 0 μmol/kg (body weight)
Section method. 19. The method of claim 14, wherein the hormone is T_3. 20. The method of claim 14, wherein the hormone is T_4. 21. The dosage of cobalt mesoporphyrin is 1 to 50
20. The method of claim 19, wherein the amount is μmol/kg (body weight). 22. The dosage of cobalt mesoporphyrin is 1 to 50
21. The method of claim 20, wherein the amount is μmol/kg (body weight). 23. A method for suppressing weight gain in an animal, if necessary, comprising parenterally administering an suppressingly effective amount of cobalt protoporphyrin or cobalt mesoporphyrin. 24. The method of claim 23, wherein cobalt protoporphyrin is administered. 25. The method of claim 23, wherein cobalt mesoporphyrin is administered. 26. The dose of cobalt protoporphyrin is 1 to 5.
Claim 24 which is 0 μmol/kg (body weight)
Section method. 27. The dosage of cobalt mesoporphyrin is 1 to 50.
26. The method of claim 25, wherein the amount is μmol/kg (body weight). 28. A method for regulating the protein-to-fat ratio in an animal comprising parenterally administering an inhibitory effective amount of cobalt protoporphyrin or cobalt mesoporphyrin. 29. The method of claim 28, wherein cobalt protoporphyrin is administered. 30. The method of claim 28, wherein cobalt mesoporphyrin is administered. 31. The dose of cobalt protoporphyrin is 1-50
30. The method of claim 29, wherein the amount is μmol/kg (body weight). 32. The dose of cobalt mesoporphyrin is 1-50μ
31. The method of claim 30, wherein the method is mol/kg (body weight). 33. A therapeutic composition for parenteral administration comprising an isotonic composition containing 1 to 25 mg/ml of cobalt protoporphyrin or cobalt mesoporphyrin.