Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/88—Liliopsida (monocotyledons)
  • A61K36/889—Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P13/00—Drugs for disorders of the urinary system
  • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P13/00—Drugs for disorders of the urinary system
  • A61P13/08—Drugs for disorders of the urinary system of the prostate
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P13/00—Drugs for disorders of the urinary system
  • A61P13/10—Drugs for disorders of the urinary system of the bladder
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P5/00—Drugs for disorders of the endocrine system
  • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones

Definitions

• This invention is related to the pharmaceutical industry and in particular to obtaining a new pharmaceutical composition and its process of obtaining from the fruits of the royal palm (Roystonea regia) to prevent and / or treat benign prosthetic hyperplasia (BPH). and prostatitis.
• the composition includes a mixture of free fatty acids and / or their esters, possibly with an extended range between 8 and 28 carbon atoms, especially those between 8 and 18 carbon atoms and more especially those saturated with a linear chain of 8, 10, 12, 14, 16 and 18 carbon atoms and monounsaturated acids of 16: 1 and 18: 1 carbon atoms. Free fatty acids are enriched from the hydrolysis of esters.
• This composition is obtained from the fruits of the royal palm by means of an obtaining process in which the fruits are initially dried and ground, and that includes a basic hydrolysis of the plant material to obtain a saponification that is subsequently subjected to a selective extraction in solvents organic or by selective extraction of the fatty acid mixture. Both procedures allow obtaining compositions with similar pharmacological properties as the extract without saponifying.
• the mixtures thus obtained are similar to the active ingredient of different pharmaceutical formulations used in the treatment of BPH and prostatitis, as well as other diseases, such as alopecia and hirsutism.
• the present invention relates to the pharmaceutical industry, since the pharmaceutical composition obtained can be used as such or in pharmaceutical formulations as a drug against BPH, prostatitis, alopecia and hirsutism.
• the prostate is a gland located immediately below the bladder and BPH is a disease that manifests in more than 50% of men over 50 years. It consists of an extension of the muscle fiber and epithelial structure of the gland that can cause a urinary obstruction that often requires surgery to relieve urinary retention symptoms, such as urination disorders, including nocturia (Madsen and Bruskewitz, Curr Opinion Nephrol Hipert 4: 455-459, 1995). While surgery, particularly transurethral resection, has been the main treatment used for a long time in patients with this disease, a variety of treatment options have recently emerged (Oesterling, New Engl. J. Med 332: 99-109, 1995; Geller et al, J. Clin.
• BPH BPH
• nocturia a nocturia
• dysuria decrease in the size and strength of urine flow
• emptying sensation incomplete and urinary retention.
• Most symptoms begin gradually, however, when the disorders progress the symptoms get worse, the application of a pharmacological therapy being necessary.
• ⁇ -adrenergic antagonists such as alfuzosin, doxazosin, terazosin, etc. (Chapple, Eur. Urol 29, 129-144, 1996) and various plant extracts have been widely used. At the moment the use of phytotherapy is common in
• Androgenic alopecia occurs in both men and women and has been seen to depend on androgens since baldness is related to the levels of the enzyme 5 ⁇ -reductase, so the androgen related to baldness is DHT, the which is produced from testosterone by the action of this enzyme.
• DHT the androgen related to baldness
• elevated levels of the enzyme 5 ⁇ -reductase have been detected in the frontal zone of bald men (Bingham KD et al, J. Endocrinology 57, 111, 1973), while men presenting the enzyme deficiency syndrome 5 ⁇ -reductase do not suffer from hair loss (Ebling FJ, Clin Endocrinol Metab 319, 1986). It has been shown that hair loss is a widely distributed phenomenon that can begin from ages after puberty, so it is necessary to develop products that prevent baldness in men and women.
• lipid extracts of Saw palmetto inhibit the hormone DHT, blocking 50% of the DHT binding sites to the receptors and the entry of the
• Saw palmetto extract used commercially for the treatment of benign BPH is a mixture of fatty acids, which also contains sterols and high molecular weight alcohols, which is obtained from the fruits of the plant by different reported methods (EPO541853, EPO492305, EPO250953, USA Patent 6,039,950, Cristoni, Phytotherapy 68, 355, 1997; DeSwaef Nat Prod Letters 7, 223, 1996).
• EPO541853, EPO492305, EPO250953, USA Patent 6,039,950, Cristoni, Phytotherapy 68, 355, 1997; DeSwaef Nat Prod Letters 7, 223, 1996 have reported such a simple and economical method as claimed in the present invention to obtain an extract of the fruits of an Arecacee, in this case, the fruits of Roystonea regia.
• the process for obtaining the composition object of the present invention is based on the drying of mature Roystonea regia fruits with a subsequent grinding of the plant until a fine powder with a particle size ⁇ 5000 ⁇ m is obtained, with or without hydrolysis basic that uses alkaline or alkaline hydroxides, toric and organic, especially those of low molecular weight and more especially those of sodium, potassium and calcium and ammonium hydroxide with subsequent extraction of plant material, followed by selective extraction in organic or supercritical solvent with CO 2 .
• Vegetable material with or without hydrolyzate is extracted using a conventional liquid solid extractor where fatty acids and / or ethyl esters are separated from the components that accompany them in the plant by selective extraction with the appropriate solvent, sought among alcohols of 1 to 3 carbon atoms and hydrocarbons of 5 to 8 carbon atoms.
• solvents we can mention methanol, ethanol, 2-propanol, hexane, pentane, isopentane, heptane and octane.
• the yield obtained is in a range between 5 and 20%.
• the mixture of acids obtained has in its composition the saturated acids of 12, 14, 16 and 18 atoms, as well as the unsaturated ones of 16: 1 and 18: 1 carbon atoms whose qualitative and quantitative composition is reported in Table 1.
• Palmitic acid (C16: 0) 10.0 - 80.0 Palmitoleic acid (C16: 1) 0.15 - 20.0
• Oleic acid (C18: 1) 3.0 - 50.0 *
• Palmitoleic acid (C16: 1) 1.9
• Palmitic acid (C16: 0) 14.8 Palmitoleic acid (C16: 1) 0.2
• Example 5 To evaluate the effect of the lipid extract of the Roystonea regia fruit, male OF1 mice were taken between 30 and 40 g in weight and adapted for 7 days to laboratory conditions with controlled temperature and humidity (25 ⁇ 2 ° C). After the adaptation period the animals were randomly distributed in different experimental groups.
• the extract of the Roystonea regia fruit was prepared in a Tween-20 / H2 ⁇ solution. The administrations were carried out orally (5mL / kg.) And the controls were administered with the vehicle.
• the deposition testosterone was dissolved in vegetable oil and administered intramuscularly (im) at the dose of 100 mg / kg. in a single administration.
• the animals were distributed randomly and the groups used were: 1) Negative control 2) Positive control (animals injected with testosterone and administered with the vehicle) 3,4 and 5) animals injected with testosterone intramuscularly (im) and administered with extract of the fruit of Roystonea regia 200, 400 and 800 mg / kg, respectively and 6) animals injected with testosterone and administered with Saw palmetto extract 400 mg / kg.
• mice were sacrificed and the abdomen opened by means of an incision in the ventral midline, the prostate was separated from the bladder and removed to be weighed.
• the comparison between the control and treated groups was made using the Mann Whitney U test. The results are presented in Table 6.
• the im injection of depot testosterone (100 mg / kg) produced a statistically significant increase in prostate weight as well as in the prostate weight / body weight ratio when compared to the negative control group.
• the administration of the object of the present invention inhibited the increase in the size of the prostate induced by the injection of testostero ⁇ a in a statistically significant way and dose dependent with a percentage of inhibition that arrives up to 92.7% at the highest dose (800 mg / kg).
• TO These doses also show a significant decrease and dose dependent on the prostate weight / body weight ratio, with a 96.6% inhibition rate at the 800 mg / kg dose.
• the substance obtained from the fruits of Roystonea regia was suspended in a Tween-20 / H2 ⁇ vehicle, administrations were performed orally (5mL / kg) and controls were administered with the vehicle.
• Testosterone propionate was dissolved in vegetable oil and administered by s.c. at the dose of 4 mg / kg daily for 14 days.
• the treated rats were distributed in 6 experimental groups: 1) Negative control + (vegetable oil); 2) Control (vehicle) + testosterone; 3, 4, 5) Fruit extract of Roystonea regia 50, 200 and 400 mg / kg. + testosterone
• the subcutaneous injection of testosterone 4 mg / kg for 14 days produced a statistically significant increase in prostate weight as well as in the prostate weight / body weight ratio when compared to the negative control group.
• the administration of the extract of the fruit of Roystonea regia and Saw palmetto (400 mg / kg) orally for 2 weeks inhibited the increase in the size of the prostate induced by the injection of testosterone in a statistically significant way with a percentage of inhibition of 41 and 58% respectively.
• Testosterone propionate was dissolved in vegetable oil and administered subcutaneously at doses of 3 and 4 mg / kg daily for 14 days.
• the Roystonea regia fruit extract was suspended in a Tween-20 / H 2 O solution. The administrations were performed orally (5mL / kg) and the controls were administered with the vehicle.
• Rats treated with testosterone 3 mg / kg were distributed in 5 experimental groups: 1) Negative control + (vegetable oil); 2) Positive control (vehicle) + testosterone; 3.4) D-004 50 and 200 mg / kg. + testosterone; 5) Saw palmetto 200 mg / kg. + testosterone
• animals treated with 4 mg / kg of testosterone were distributed in 6 experimental groups: 1) Negative control + (vegetable oil); 2) Control (vehicle) + testosterone; 3, 4, 5) Roystonea regia extract 50, 200 and 400 mg / kg. + testosterone; 5) Saw palmetto 400 mg / kg. + testosterone All treatments were administered for 14 days.
• the results are presented in Tables 8 and 9. TABLE 8. Effect of Roystonea regia lipid extract in male Sprague Dawley rats with induced prostatic hyperplasia Treatment Dose
• the rabbits were distributed in 4 groups of 5 rabbits each, the rabbits of group 1 received a daily administration of 400 mg of Roystonea regal extract once a day, the rabbits of group 2 received vehicle once a day, the rabbits of the group 3 received 400 mg of Roystonea regia extract divided into two 200 mg portions and rabbits in group 4 received the vehicle twice a day, as did group 3.

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