Method of Treating Proteinuria in Pregnancy

Abstract

A therapeutic agent for the treatment of toxemia, preeclampsia and eclampsia and a method for preparing the therapeutic agent are disclosed. The therapeutic agent is a stable pharmaceutical preparation containing, but not limited to, digestive/pancreatic enzymes. The therapeutic agent may be manufactured by a variety of encapsulation technologies. Delivery of the therapeutic agent may be made orally, through injection, by adherence of a medicated patch or by other methods. Further, a method of using the presence of chymotrypsin in the maternal GI tract as a biomarker, to determine the likelihood of developing preeclampsia, a pregnancy induced hypertension, and eclampsia/toxemia is disclosed.

Claims

1. A method for treating an individual exhibiting one or more symptoms of preeclampsia, the method comprising administering a therapeutically effective amount of digestive enzymes to the individual.

2. The pharmaceutical preparation of claim 1, wherein the digestive enzyme is selected from the group consisting of: amylase, lipase, protease, and a combination thereof.

3. The pharmaceutical preparation of claim 1, wherein the digestive enzyme is further selected from the group consisting of: chymotrypsin, trypsin, pancreatin, papaya, papain, and a combination thereof.

4. The pharmaceutical preparation of claim 1, wherein the enzymes are derived from a source selected from the group consisting of animal enzymes, plant enzymes, synthetic enzymes, and a combination thereof.

5. The pharmaceutical preparation of claim 1 wherein the preparation is manufactured using a technology selected from the group consisting of enteric coating, lipid encapsulation, direct compression, dry granulation, wet granulation, and a combination thereof.

6. The pharmaceutical preparation of claim 1, wherein the preparation is administered orally via a dosage formulation selected from the group consisting of: pills, tablets, capsules, microcapsules, mini-capsules, time released capsules, mini-tabs, sprinkles, and a combination thereof.

7. The pharmaceutical preparation of claim 2, wherein the amount of amylase ranges from 10,000 to 60,000 USP units/mg.

8. The pharmaceutical preparation of claim 2, wherein the amount of protease ranges from 10,000 to 70,000 USP units/mg.

9. The pharmaceutical preparation of claim 2, wherein the amount of lipase ranges from 4,000 to 30,000 USP units/mg.

10. The pharmaceutical preparation of claim 3, wherein the amount of pancreatin ranges from 2,000 to 6,000 USP units/mg.

11. The pharmaceutical preparation of claim 3, wherein the amount of chymotrypsin ranges from 2 to 5 mg.

12. The pharmaceutical preparation of claim 3, wherein the amount of papain ranges from 3,000 to 10,000 USP units/mg.

13. The pharmaceutical preparation of claim 3, wherein the amount of papaya ranges from 30 to 60 mg.

14. The pharmaceutical preparation of claim 3, wherein the amount of trypsin ranges from 60 to 100 mg.

15. The pharmaceutical preparation of claim 1, wherein a symptom of the preeclampsia is ameliorated.

16. The pharmaceutical preparation of claim 1 wherein the symptom of the preeclampsia is selected from the group consisting of: hypertension, proteinuria, and a combination thereof.

17. A method for treating an individual exhibiting preeclampsia or eclampsia and having a subnormal amount of fecal chymotrypsin, the method comprising administering a therapeutically effective amount of a pharmaceutical preparation comprising digestive enzymes to the individual, wherein the digestive enzymes comprise an amylase, a lipase, a protease, or a combination thereof, whereby the preeclampsia or eclampsia is treated.

18. The method of claim 17, wherein the pharmaceutical composition comprises one or more proteases, wherein the one or more proteases comprise chymotrypsin or trypsin.

19. The method of claim 17, wherein the digestive enzymes are provided as pancreatin.

20. The method of claim 17, wherein the digestive enzymes are obtained from a source selected from the group consisting of animal enzymes, plant enzymes, synthetic enzymes, and a combination thereof.

21. The method of claim 17, wherein the pharmaceutical preparation is manufactured using a technology selected from the group consisting of enteric coating, lipid encapsulation, direct compression, dry granulation, wet granulation, and a combination thereof.

22. The method of claim 17, wherein the pharmaceutical preparation is administered orally via a dosage formulation selected from the group consisting of a pill, a tablet, a capsule, a microcapsule, a mini-capsule, a time released capsule, a mini-tab, a sprinkle, and a combination thereof.

23. The method of claim 17, wherein the amount of amylase ranges from 10,000 to 60,000 USP units/dose.

24. The method of claim 17, wherein the amount of protease ranges from 10,000 to 70,000 USP units/dose.

25. The method of claim 17, wherein the amount of lipase ranges from 4,000 to 30,000 USP units/dose.

26. The method of claim 19, wherein the amount of pancreatin ranges from 2,000 to 6,000 USP units/dose.

27. The method of claim 18, wherein the amount of chymotrypsin ranges from 2 to 5 mg/dose.

28. The method of claim 18, wherein the amount of trypsin ranges from 60 to 100 mg/dose.

29. A method for treating an individual exhibiting preeclampsia or eclampsia, the method comprising administering a therapeutically effective amount of a pharmaceutical preparation comprising digestive enzymes to the individual, wherein the digestive enzymes comprise an amylase, a lipase, a protease, or a combination thereof, wherein the pharmaceutical preparation is manufactured using a technology selected from the group consisting of enteric coating, lipid encapsulation, direct compression, dry granulation, wet granulation, and a combination thereof, whereby the preeclampsia or eclampsia is treated.

30. A method for treating an individual exhibiting preeclampsia or eclampsia, the method comprising administering a therapeutically effective amount of a pharmaceutical preparation comprising digestive enzymes to the individual, wherein the digestive enzymes comprise an amylase, a lipase, a protease, or a combination thereof, wherein the pharmaceutical preparation is administered orally, via injection or a medicated patch, whereby the preeclampsia or eclampsia is treated.

31. A method for treating an individual exhibiting preeclampsia or eclampsia, the method comprising administering a therapeutically effective amount of a pharmaceutical preparation comprising digestive enzymes to the individual, wherein the digestive enzymes comprise an amylase, a lipase, a protease, a cellulase, a papaya, a papain, a bromelain, a chymotrypsin; and a hydrolase, whereby the preeclampsia or eclampsia is treated.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0026] FIG. 1 is a table illustrating the changes in blood pressure, both diastolic and systolic, urine protein level, and fecal chymotrypsin level in pregnant women with preeclampsia that were administered pancreatic enzymes.

[0027] FIG. 2 is a graph illustrating the changes in blood pressure of preeclamptic women over a 30 day period after being administered pancreatic enzymes.

[0028] FIG. 3 is a graph illustrating the changes in urine protein level of preeclamptic women over a 30 day period after being administered pancreatic enzymes.

[0029] FIG. 4 is a chart illustrating the fecal chymotrypsin levels in seventeen pregnant women from week 12 of pregnancy through week 40 of pregnancy.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0030] Since placental delivery reverses the symptoms of preeclampsia, it suggests that the placenta has a central role in the condition. Additionally, women with increased placental tissue for gestational age, or those with hydatidiform moles and twin pregnancies, have an increased prevalence of preeclampsia. This leads one to consider the possibility that substances, such as human chorionic gonadotropin, which is present in an increased amount in a hydatidiform mole, may be involved. This link between formation of the placenta and the development of preeclampsia is key.

[0031] The formation of the syncytial trophoblast, and its secretion of steroid hormones keeps the levels of human chorionic gonadotropin low, and thereby reduces the likelihood of developing preeclampsia. The syncytial trophoblast further proliferates to form a highly specialized trophoblast, known as an extravillous trophoblast. The extravillous trophoblast bores through the endometrium, extending to the decidua and myometrium. These extravillous trophoblasts continue their invasion into the spiral arterioles and replace the endothelial and muscular linings of the uterine arterioles, leading to vasodilation of the uterine vasculature. This change ensures a continued low resistance system, which potentiates maternal blood flow to the intervillous space and maintains adequate perfusion of the developing fetus.

[0032] The mechanism by which the cellular trophoblast is reduced in its proliferation so that the syncytial trophoblast may take over is the presence of proteolytic enzymes, especially that of chymotrypsin. The maternal proteases, especially that of chymotrypsin, are able to restrain the proliferation of the cellular trophoblast and the overproduction of human chorionic gonadotropin.

[0033] In one embodiment, a stable preparation of digestive/pancreatic enzymes is formed into a dosage formulation containing a therapeutically effective amount of a protease, an amylase, and/or a lipase. The formulation may include additional enzymes, such as pancreatin, chymotrypsin, trypsin, papain and/or papaya. Other combinations of digestive enzymes may also be used. These enzymes can be in the form of animal or plant derivatives, natural or synthetic.

[0034] The following outlines a formulary for digestive/pancreatic enzymes for preeclampsia/toxemia:

[0035] Amylase 10,000-60,000 U.S.P.

[0036] Protease 10,000-70,000 U.S.P.

[0037] Lipase 4,000-30,000 U.S.P.

[0038] Pancreatin 2,000-6,000 U.S.P.

[0039] Chymotrypsin 2-5 mg

[0040] Trypsin 60-100 mg

[0041] Papain 3,000-10,000 U.S.P. units/mg

[0042] Papaya 30-60 mg

[0043] The dosage formulation may be administered by an oral preparation including, but not limited to, an encapsulated tablet, mini-tabs, microcapsule, mini-capsule, time released capsule, sprinkle or other methodology. In one embodiment, the oral preparation is encapsulated using PROSOLV technology. Alternatively, the oral preparation may be encapsulated using enteric coating, lipid encapsulation, direct compression, dry granulation, wet granulation, and/or a combination of these methods.

[0044] In a study conducted by the inventor, six women diagnosed with preeclampsia in weeks 28-34 of pregnancy were examined. Each was administered pancreatic enzymes, including lipases, amylases and proteases, within two days of their diagnosis of preeclampsia for the duration of their pregnancy, while being monitored by their obstetricians. The results of the study are found in FIG. 1, which illustrates the changes in the women's blood pressure, both diastolic and systolic, urine protein level, and fecal chymotrypsin levels.

[0045] As seen in FIG. 2, it is clear from the results that the blood pressures of the pregnant women were reduced significantly over the 30 days of administration of the pancreatic enzymes. In every case, their blood pressures returned to normal, which is usually 120/80. In some cases, the reversion to a normal blood pressure reading occurred within 15 days.

[0046] Further, the levels of protein in their urine also reverted to normal within 30-35 days as seen in FIG. 3. Proteinuria is diagnosed by examining the urine through a simple urinalysis. Normal urine has very small amounts of protein present. Larger amounts are usually reported as 1+ to 4+.

[0047] In another study, shown in FIG. 4, seventeen women that were pregnant for the first time (primipara) that were in their first trimester were administered a fecal chymotrypsin test every other week from week 12 to week 40 of their pregnancy. One woman, subject 6, developed preeclamptic symptoms, and her fecal chymotrypsin test became abnormal one week prior to the diagnosis of preeclampsia.

[0048] Fecal chymotrypsin is a sensitive, specific measure of proteolytic activity. Normal levels of chymotrypsin are considered be greater than 8.4 U/gram. Decreased values (less than 4.2 U/gram) suggest diminished pancreatic output (pancreatic insufficiency), hypoacidity of the stomach or cystic fibrosis. Elevated chymotrypsin values suggest rapid transit time, or less likely, a large output of chymotrypsin from the pancreas.

[0049] For the fecal chymotrypsin test, a stool sample was collected from each of the subjects. Each stool sample was analyzed using an enzymatic photospectrometry analysis to determine the level of fecal chymotrypsin in the stool. Alternatively, other methods, such as the colorimetric method, use of substrates, use of assays, and/or any other suitable method may be used to measure the fecal chymotrypsin levels. The levels of fecal chymotrypsin in the samples of the primipara pregnant women were compared to the levels of fecal chymotrypsin in pregnant women not diagnosed with preeclampsia to determine if the primipara pregnant women would benefit from the administration of digestive enzymes.

[0050] The foregoing description of the embodiments of the invention has been presented for the purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed. Many modifications and variations are possible in light of this disclosure. It is intended that the scope of the invention be limited not by this detailed description, but rather by the claims appended hereto.