JP3034032B2 - Intestinal disorders - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to insulin-like growth factor-I (IGF-I).
And analogs thereof. More specifically, the present invention provides
It relates to the use of IGF-I and analogs thereof to treat disorders of intestinal function, for example with regard to the effects of intestinal diseases.

IGF-I is a small protein that has been found to promote cell growth in culture. Animal growth
It is also promoted in pituitary failure, normal and catabolic states.
Kidney function is also improved. Based on these studies, IGF-
I in humans to (1) treat growth hormone deficiency, (2) suppress body protein loss in catabolic states following burns, infections or other trauma, and (3) suffer from kidney disease It is thought that it can be applied effectively as a treatment for patients who have it.

Many human diseases cause the subject's intestinal tissue to be in smaller quantities than required for normal digestion or absorption, or diseased but normal length intestine that is impaired in digestion or absorption It has become. Examples of human diseases that fall into these two categories include short bowel syndrome, chronic ulcerative bowel disease, inflammatory bowel diseases such as colitis and Crohn's disease, and necrotizing enterocolitis in infants .

IGF-I is not known in the prior art to increase the growth or function of the abdominal gastrointestinal tract, a cell type consisting of the stomach, duodenum, jejunum, ileum, cecum and colon. It is these areas of the intestine that are affected by the disease. Intestinal tissues contain the receptor for IGF-I (see, eg, M. Laburthe et al., Am. J. Phy.
siol., 254 , G457, 1988; DJPillion et al., Am. J. Physiol., 2
57 , E27, 1989; H. Werner et al., Pro.
Natl. Acad. Sci. USA, 86 , 7451, 1989), which is known to synthesize IGF-I or IGF-I messenger RNA under certain conditions (eg, P.K. PKLund et al., J. Biol. Chem., 261 , 14539, 1986; AJD'Ercole et al., Pediat.
r.Res., 20, 253, 1986; HA Han
sson) et al., Histochemisty, 89 , 403, 1988; W. L. Lowe, Jr., J. Clin. Inves.
t., 84 , 619, 1989).

Previously, IGF-I has been administered to dwarf mice, hypophysectomized rats, diabetic rats, fasted mice and rats, normal rats, mini-poodles and normal human subjects.

The amount of IGF-I was also increased by insertion of the IGF-I expression transgene into mice. In many of these studies, IGF-I treatment increased body growth. IGF−
It was noted that an undesirable side effect of high doses of I was hypoglycemia. However, none of the reported studies describe the effect of IGF-I on the abdominal gastrointestinal tract. For example, in one study in which transgenesis overexpressed IGF-I and resulted in substantial body growth in transgenic mice, the duodenal fraction weight was the same as in IGF-deficient animals (R. Boehringer). (RRBehringer) et al., Endoc
rinology, 127 , 1033, 1990). In another study, administration of low doses of IGF-I to infant rats did not change the weight of the gastrointestinal tract (GP Young (GPYoun).
g) et al., Digestion, 46S2 , 240, 1990). In particular, there is no report on the increase in intestinal weight after administration of IGF-I.

Accordingly, it is an object of the present invention to overcome or at least mitigate one or more of the problems associated with the prior art.

In a first embodiment of the method of the present invention, animals, including humans with impaired intestinal function, are mammals, preferably human IGF-
I by treating.

Accordingly, in a first aspect of the present invention, there is provided a method of treating intestinal dysfunction in an animal, including a human, wherein the patient undergoing treatment is treated with mammalian insulin-like growth factor-I (IGF-I).
Or administering an effective amount of a peptide analog thereof.

As used herein, the term "disorder of intestinal function" means one or more disorders of the stomach, duodenum, jejunum and ileum, and colon. These disorders may relate to gastrointestinal disorders and / or surgical treatment. Thus, as used herein, in general terms with respect to the treatment of gastrointestinal disorders, the treatment of disease-free gastrointestinal tracts, some of which have been surgically removed, and those of the rest of the body that promote growth. Should be understood to include the case where is free.

As used herein, the term "peptide analog" refers to one or more of, or from, peptide analogs relating to Applicants' International Patent Applications PCT / AU88 / 00246 and PCT / AU88 / 00485. Derived fusion proteins, including those described in International Patent Application No. PCT / AU90 / 00210, the entire disclosure of which is hereby incorporated by reference.

An effective amount of mammalian IGF-I or an analog of IGF-I is
It is defined as that required to increase the weight of intestinal tissue by more than about 20% as compared to the weight of intestinal tissue before treatment.

Applicants have surprisingly found that IGF-I and its analogs increase the weight of the stomach, duodenum, jejunum and ileum, and the colon as well as the total intestine. Of particular importance, these effects on growth include: (a) animals whose intestinal function has been significantly reduced in advance by surgical removal of a substantial portion of the jejunum and ileum; (C) animals induced catabolism by administration of glucocorticoids to induce diabetes by a medicinal product, streptozotocin, such that intestinal growth is enhanced above that of growth in which the effect of IGF-I has already been promoted; And (d) animals that have reduced kidney function, which is found to occur in animals under certain conditions, including:

Glucocorticoids are administered to humans as a current treatment for inflammation characteristic of several types of intestinal diseases, so that intestinal growth is partially affected by IGF-I or an analog thereof even in the presence of glucocorticoids. It is surprising and advantageous to find this fact that it can be restored.

In a preferred embodiment of the present invention, the peptide analog IGF-I is administered to a mammal, preferably a human. Preferably, the peptide analog is one in which one to five amino acid residues are missing from the N-terminus of mammalian IGF-I. Preferably, three amino acid residues are missing therefrom. Such peptide analogs are known as deaths (1-
3) It is called IGF-I.

Alternatively, the peptide analog is an analog in which at least a glutamic acid residue has been deleted from the N-terminus of mammalian IGF-I in position 3 and optionally replaced by a different amino acid residue. Preferably, the analog is one in which a glutamic acid residue has been replaced by an arginine residue.

More preferably, the peptide analog is And has been shown to have a Cys residue usually at position 6 from the N-terminus.

In yet another embodiment, the peptide analog comprises approximately the first about 100 of methionine porcine growth hormone.
A first amino acid sequence comprising the N-terminal amino acids or fragments thereof, and a second amino acid sequence of mammalian insulin-like growth factor-I or an analog thereof, wherein It is a fusion protein that includes linked ones.

Preferably, the first amino acid sequence comprises approximately the first about 46, more preferably the first 11 N-terminal amino acids of methionine porcine growth hormone or a fragment thereof.

IGF-I analogs are commonly owned in International Application P
CT / AU86 / 00246, including Des (1-3) IGF-I, which is incorporated herein by reference and cultured at lower doses than the required dose of IGF-I. It has been shown to increase cell growth. In the development of the present invention, des (1-3) IGF-I is used in the treatment of disorders of intestinal function, since analogs with lower potency than the concentration of IGF-I itself increase intestinal tissue growth relatively. It has been surprisingly found that this potency increases in vivo.

IGF-I analogs are commonly owned in International Application P
Encompasses fusion proteins MpGH according ^{(11) VN / R 3 IGF} -I (LR 3 abbreviated) as Example 13 of CT / AU90 / 00210 Pat, this specification is included herein by reference ,and
It has been shown that doses lower than the required dose of IGF-I increase the growth of cultured cells. In the present invention, IGF-
In the treatment of disorders of intestinal function, LRs are used in the treatment of disorders of intestinal function, since analogs at lower concentrations than I itself increase intestinal tissue growth relatively.
It was surprisingly shown that the potency of ³ increased.

In particular, this method involves the use of IGF-I or IGF-I in human subjects.
Although adapted for treatment with an analog of I, the method is also applicable veterinarily to animals with intestinal disease.

Thus, in another aspect, the present invention provides: (a) a mammal, preferably a human, an effective amount of IGF-I or a peptide analog thereof; and (b) a pharmaceutically or veterinarily acceptable diluent,
A pharmaceutical or veterinary composition for treating bowel dysfunction, comprising a carrier or excipient.

In a preferred form, the invention is a pharmaceutical or veterinary composition, wherein the IGF-I or analog of IGF-I is about 10-200.
Provided is one present in an amount sufficient to provide a dosage of 0, preferably 100-1000 μg / kg body weight / day.

In a further preferred embodiment of the invention, there is provided a method of treating intestinal dysfunction, comprising: (a) an effective amount of a mammalian, preferably human, IGF-I or a peptide analog thereof; Acceptable diluent,
Administering a pharmaceutical or veterinary composition comprising a carrier or excipient to a patient undergoing treatment.
A method is provided which comprises administering intravenously, subcutaneously, intramuscularly or intestine at a dose of about 10-2000, preferably 100-1000 μg / kg body weight / day. Treatment may last for a period of about 1-60 days, preferably about 5-30 days.

Dosage amount, interval and duration of treatment can be adjusted according to the degree of enteric disease and the route of administration. Care should be taken to monitor blood glucose to prevent hypoglycemia.

The dose and interval for the administration of Des (1-3) IGF-I and related analogs are set at levels adjusted relative to the relative potency of the analog relative to the potency of IGF-I itself. can do. For example, levels of des (1-3) IGF-I or LR ³ is below the efficacy of the total IGF-I peptides by increased potency of proportionally des (1-3) IGF-I or LR ^3. Des (1-3) doses of IGF-I LR ³ 50~500μg / kg body weight / day being preferred.

In yet another aspect of the present invention, there is provided the use of mammalian insulin-like growth factor-I (IGF-I) or a peptide analog thereof for the manufacture of a pharmaceutical or veterinary formulation for the treatment of intestinal dysfunction. You.

Pharmaceutical or veterinary preparations can be prepared using conventional techniques.

The benefits and parameters of the present invention will be described in further detail with respect to the accompanying examples. However, the following description is to be understood as being illustrative only, and should not be considered as limiting the generality of the above description.

Example 1 IGF on gastric growth of growth hormone deficient 1it / 1it mice
Effect of -I and Death (1-3) IGF-I Six-week-old 1it / 1it mice were individually housed, weighed daily, and substantially stopped growing by eight weeks of age. .

The mice were then randomly divided into 5 groups according to body weight and gender: (a) 1 part HCl (10 mmol / l) and potassium phosphate (50 mmol / l), NaCl (150 mmol / l) and 0.1 % Human serum albumin, pH
7.4 (diluent) 120 μl of a sterile solution containing 9 parts of diluent, (b) 120 μl of diluent containing 3 μg of IGF-I, (c) diluent 1 containing 3 μg of des (1-3) IGF-I
(D) 120 μl of a diluent containing 30 μg of IGF-I, or (e) diluent 1 containing 30 μg of des (1-3) IGF-I
Was injected daily for 20 days. Each dose was administered subcutaneously as two injections subcutaneously, one at 9-10 am and another at 4-5 pm. Animals were weighed every seven days and their height was measured.

On day 21, animals were sacrificed by an overdose of anesthetic,
The tissue was removed and weighed. The body weight, animal height (including tail) and stomach weight are shown in Table 1 below. Values are mean ±
Standard error, statistical significance from diluent-treated control animals was shown as * P <0.05; ** P <0.01. The number of animals is indicated in parentheses.

Since the initial weight was 10 g for each group, the daily dose was about 300 peptides per kg body weight each.
μg and 3000 μg.

The weight of the stomach, expressed as a percentage of the diluent group, is
105% at 300 μg and 3000 μg / kg body weight / day of IGF-I
And 123%, respectively, and death (1-3) IGF-1
110% and 123 at 300 μg and 3000 μg / kg body weight / day
%Met.

Example 2 IGF-I on intestinal weight of dexamethasone treated rats
And is des (1-3) Effect average body weight of the IGF-I LR ³ is 152g (range 138~164g), male Fu de consent Stars, which had been placed in a metabolism cage (Hooded Wis
ter) An Alzet model 2001 osmotic pump was inserted subcutaneously under the scapula into the rat under ether anesthesia. One pump delivers 20 μg / day dexamethasone and the other pump (a) 0.1 M acetic acid as diluent, (b) 111 μg / day IGF-I, (c) 278 μg / day IGF -I, (d) IGF-I at 695 μg / day, (e) Death (1-3) GF- at 44 μg / day, (f) Death (1-3) IGF-I at 111 μg / day, (g) 278μg / day of death (1-3) IGF-I, ( h) 44μg / day of LR ^3, (i) 111μg / day of LR ^3, was fed the LR ^3, of (j) 278μg / day.

Animals were kept in metabolic cages for 7 days, and body weight, food and nitrogen intake and nitrogen excretion were measured daily. After this period, the animals were sacrificed by phlebotomy under anesthesia and the gastrointestinal tract was removed from the stomach into the colon and separated into the stomach, duodenum, ileum and jejunum, cecum and colon. Food or fecal contents were removed from all parts and weighed.

The body weight and weight of various parts of the gastrointestinal tract are shown in Table 2 as the mean ± sem. Statistical significance from the group treated with diluent was * P <0.05; ** P <0.01; *** P <0.
Shown as 001. There were 6 animals in each group.

The weight of the whole intestine from the stomach to the colon is determined by IGF-I
-3) dosage for IGF-I and LR ³ - as a fraction of total body weight in the form of the response curve, shown in Figure 1.

In the central part of the ileum and colon, cut the part vertically,
It was scraped off and the mucosal layer was removed. The weight of this layer was expressed as a percentage of mucosa + muscle. The protein content of the same part of the ileum was measured and expressed as mg / g wet weight of tissue. These values are shown in Table 3 as mean ± standard error. Statistical significance from animals treated with diluent was not obtained using ANOVA (P> 0.05).

In this example, IGF-I, death (1-3) IGF-I or
Weight of various parts of the intestine dexamethasone treated rats after administration of LR ³ is shown to increase significantly. Effect depends dose greater in death (1-3) IGF-I or LR ³ in the same doses as the IGF-I.

Increasing growth occurs primarily by swelling of the intestinal cross-section, as the length of each segment does not increase or increases only slightly.

It is clear from FIG. 1 that the increase in intestinal weight proportionately outweighs the increase that occurs for body weight.

Since the weight percentage exhibited by the mucosa is not affected by IGF treatment, both the mucosal and muscular portions of the jejunum and colon show increased growth.

Growth occurs by an increase in tissue protein, as the protein content percentage of the jejunum and colon does not change with IGF treatment.

Example 3 Quantitative histology of duodenum from rats in Example 2 The midpoint of the duodenum from a given animal in Example 1 was fixed by Boin fixation, dehydrated, embedded, cut in cross section, hematoxylin and eosin. For quantitative histological analysis. All animals in groups (a), (c), (g) and (j) of Example 2 were treated to determine villus height, crypt depth, mucosal area, submucosal area, external muscle Area and total cross-section measurements were obtained. For each duodenum, 30 villous heights, 30 crypt depths and 8 area measurements were averaged to give representative values. Mean ± SEM
(N = 6) is shown in Table 4.

In this example, IGF-I at a dose of 278 μg / day, death (1
-3) IGF-I or growth of the duodenum produced by LR ³ shows that with increased statistically significant (P <0.01) the cross-sectional area. This increase is mainly due to an increase in the mucosal area, although the muscle layer also increases. Villi also increase in height, which makes up much of the mucosa and plays an important role in digestion and absorption.

Example 4 Effect of IGF-I and Des (1-3) IGF-I on intestinal weight of rats treated after partial resection of the jejunum and ileum, with an average body weight of 175 g (range 160-193 g) and Old Sprague Dawl
ey) An Alzette 2001 osmotic pump was inserted into the rat as in Example 2. The doses of the growth factors were 170 μg / day for IGF-I and des (1-3) IGF-I and 1 GF
For -I, the high dose was 425 μg / day. The pump was inserted subcutaneously using tribromomethanol anesthesia in amylene hydrate and aseptic technique, while the jejunum and ileum were exposed by midline incision. Middle 80 of these parts of the intestine
%, Starting 10cm from the ligament of Treitz and 10cm from the ileocecal valve
Taken out. The intestine and abdominal cavity are penicillin
(U / ml). To further prevent infection, the animals were injected with 0.6 ml procaine penicillin before and four days after surgery. Animals were returned to metabolism cages with free access to food and water. Body weight, food intake, nitrogen intake and nitrogen production were measured daily.

Seven days after treatment, the animals were bled under anesthesia and sacrificed, and the gastrointestinal tract from the stomach to the colon was removed and separated into the stomach, duodenum, remaining jejunum and ileum, colon and cecum. Food or fecal contents were removed from all collected parts of the intestine and weighed. The body weights and weights of various parts of the intestine are shown in Table 5 as mean ± standard error. Statistical significance from the group treated with diluent is shown as * P <0.05; ** P <0.01. 7 in diluent and death (1-3) IGF-I group
Animals, 6 in the low-dose IGF-I group and 5 in the high-dose IGF-I group.

This example shows that Des (1-3) IGF-I and a 2.5-fold dose of IGF-I produce a significant growth effect in the intestine. Death (1-3) IGF same as the dose of IGF-I
No statistically significant effect was obtained with the dose of -I.

Total intestinal weight, excluding residual jejunum and ileum, expressed as a percentage of the diluent group was 113 mg for IGF-I 170 μg / day.
%, 131% at 425 μg / day of IGFPI and death (1-3) I
It was 125% at 170 µg / day of GF-I.

Example 5 IGF-I, Des (1-(-) on intestinal growth of diabetic rats
3) Effects of IGF-I and MPGH (11) VN / R ³ IGF-I (LR ³ ) Male hooded Wistar rats weighing about 150 g
Streptozotocin was injected intraperitoneally at a dose of 70 mg / kg and transferred to metabolic cages. Diabetes was confirmed by measuring blood glucose. After 7 days (average weight 162g),
Implanting the osmotic pump into the animal in exactly the same way as in Example 1,
Exactly the same dose as in Example 1 was delivered. After 7 days of treatment, the animals were sacrificed and the following intestinal organs were weighed:
Stomach, duodenum, ileum and jejunum, and colon. These values are shown in Table 6, and the total intestinal weight is shown in FIG. Each value is
Mean ± SEM for 6 animals. Statistical significance (ANOVA: least significant difference) was determined for diabetic rats treated with * P <0.05, ** P <0.01, *** P <0.
Indicated by 001.

These results indicate that IGF-I and low dose of death (1
-3) IGF-I or LR ³ is shows causing substantial growth effects stomach, ileum and jejunum, against colon and Socho weight. The effect on the duodenum is rather small.

The response of IGF in diabetic rats is particularly important since untreated animals already have heavy intestinal weight as a result of bulimia associated with this condition. For example, another group of animals whose diabetes was treated with insulin had an ileum and jejunum weight of 5.08 ± 0.29 g. This is lower than the diluents etc. in Table 5, despite the fact that the animals treated with insulin are much heavier.

Example 6 Effect of IGF-I and Des (1-3) IGF-I on Intestinal Weight of Rats After Partial Nephrectomy Partial kidney disease was induced by male Sprague-Dawley rats by near-complete nephrectomy in two stages. (95-125 g). This involves ischemia of at least half of the left kidney by connecting the terminal branches of the left renal artery (day 0), one week later a right nephrectomy is performed, and the right jugular vein is also cannulated at this time. This was done by flank incision by doing (day 7). Partially nephrectomized rats were selected on day 14 for inclusion in the study period based on detectable proteinuria and urine volume and serum urine levels at least twice that of sham-operated control animals. 16
On the day, treatment was initiated with a mini-osmotic pump (Alzette 2001, Alza Co., Palo Alto, CA) implanted subcutaneously in the dorsal thorax under halothane anesthesia. Rats from which the kidneys were removed were randomly treated with diluent (0.1 M acetic acid) and low-dose IGF-I (170 μg /
Days), high-dose IGF-I treatment (425 μg / day), or death (1-3) IGF-I treatment (170 μg / day).
The average body weight at the time of pump insertion was 193 g. Animals were sacrificed on day 23 and intestinal weight was determined as in Example 2. These are shown in Table 7. Statistical significance from animals treated with diluent is indicated by * P <0.05, ** P <0.01.

This example demonstrates that treatment with IGF-I or Des (1-3) IGF-I for 7 days in rats treated by partial nephrectomy increases intestinal weight.

Finally, it should be understood that various other modifications and / or changes can be made without departing from the spirit of the invention described herein.

Continuation of the front page (72) Inventor Reid Leanna Kristin 5068 South Australia, Kensington, High Street 4/46 (56) References JP-A-64-66199 (JP, A) International Publication 89/10129 ( WO, A1) International Publication 89/5822 (WO, A1) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 37/36 C07K 14/65 CA (STN) REGISTRY (STN) WPIL (DERWENT)

Claims (17)

(57) [Claims] 1. A mammalian insulin-like growth factor-I, or a peptide analog thereof, which is a peptide fragment of insulin-like growth factor-I, wherein one or more amino acids are deleted and / or substituted. And insulin-like growth factor-I selected from the group consisting of insulin-like growth factor-I or a fusion peptide comprising said peptide fragment.
A human or veterinary medicament for treating intestinal dysfunction by increasing the weight of intestinal tissue, comprising an effective amount of said peptide analog having the same pharmacological effect as described above. 2. The mammalian insulin-like growth factor-I.
Is the human insulin-like growth factor-I. 3. The mammalian insulin-like growth factor-I.
Or about 10-5000 μg / kg body weight /
3. The medicament of claim 1 or 2, wherein the medicament is included in an amount sufficient to provide a daily dose. 4. The mammalian insulin-like growth factor-I.
The agent according to claim 1, wherein the peptide analog has no 1 to 5 amino acid residues from its N-terminus. 5. The mammalian insulin-like growth factor-I.
5. The agent according to claim 4, wherein the peptide analog has no three amino acid residues from its N-terminus. 6. The mammalian insulin-like growth factor-I.
2. The agent of claim 1, wherein at least the glutamic acid residue is missing at the N-terminus of position 3 or substituted at that position with a different amino acid residue. 7. The drug according to claim 6, wherein the glutamic acid residue is substituted by an arginine residue. 8. The mammalian insulin-like growth factor-I.
Is a peptide analog of The agent of claim 6, having an N-terminal sequence selected from: 9. The mammalian insulin-like growth factor-I.
A first amino acid sequence comprising the first about 100 N-terminal amino acids of methionine porcine growth hormone or a fragment thereof; and a second amino acid of mammalian insulin-like growth factor-I or an analog thereof. The agent according to claim 1, which is a fusion protein having a sequence linked to the C-terminus of the first amino acid sequence. 10. The method according to claim 10, wherein said first amino acid sequence comprises the first about 46 of methionine porcine growth hormone or a fragment thereof.
10. The medicament of claim 9, which comprises N N-terminal amino acids. 11. The method according to claim 11, wherein the first amino acid sequence comprises about the first 11 amino acids of methionine porcine growth hormone or a fragment thereof.
10. The medicament of claim 9, which comprises N N-terminal amino acids. 12. The insulin-like growth factor of the mammal.
4. The peptide analog of I, which is included in an amount sufficient to provide a dosage of about 50-500 [mu] g / kg body weight / day.
12. The drug according to any one of 11 above. 13. A method for treating intestinal dysfunction in a non-human animal by increasing the weight of intestinal tissue, wherein the subject to be treated is a mammalian insulin-like growth factor-I or a peptide thereof. An analogous peptide fragment of insulin-like growth factor-I,
An insulin-like growth factor selected from the group consisting of a peptide fragment in which one or more amino acids may be deleted and / or substituted, and insulin-like growth factor-I or a fusion peptide containing the peptide fragment. A method comprising administering an effective amount of said peptide analog having a pharmacological effect similar to I. 14. The mammalian insulin-like growth factor.
About 10 to 5000 μg / kg body weight /
14. The method of claim 13, wherein the method is administered in a daily amount for about 1 to 60 days. 15. (a) Mammalian insulin-like growth factor-I or a peptide analog thereof, which is a peptide fragment of insulin-like growth factor-I, wherein one or more amino acids are deleted and / or substituted. Said peptide fragment selected from the group consisting of a peptide fragment which may be and insulin-like growth factor-I or a fusion peptide comprising said peptide fragment, and which has the same pharmacological effect as insulin-like growth factor-I An effective amount of the body; and (b) a pharmaceutically or veterinarian for treating intestinal dysfunction by increasing the weight of intestinal tissue, including its pharmaceutically or veterinarily acceptable diluent, carrier or excipient. Composition. 16. The mammalian insulin-like growth factor.
16. The method of claim 15, wherein I or an analog thereof is present in an amount sufficient to provide a dosage of about 10-5000 [mu] g / kg body weight / day.
A pharmaceutical or veterinary composition according to claim 1. 17. A method for treating intestinal dysfunction in a non-human animal by increasing the weight of intestinal tissue, comprising: (a) mammalian insulin-like growth factor-I, or a peptide analog thereof. And insulin-like growth factor-
I is a peptide fragment selected from the group consisting of a peptide fragment of which one or more amino acids may be deleted and / or substituted, and insulin-like growth factor-I or a fusion peptide comprising said peptide fragment, and A veterinary composition comprising: an effective amount of said peptide analog having a pharmacological effect similar to insulin-like growth factor-I; and (b) its veterinarily acceptable diluent, carrier or excipient. About 10 to 50
A method comprising administering intravenously, subcutaneously, intramuscularly or intestine at a dose of 00 μg / kg body weight per day for about 1 to 60 days.