TWI516279B - Formulas comprising highly soluble elements and vitamin for the prevention and amelioration of osteoporosis - Google Patents

Description

Formulations containing high soluble elements and vitamins for the prevention and improvement of osteoporosis Field of invention

This application claims priority to U.S. Patent Application Serial No. 12/845,301, filed on July 28, 2010. The U.S. Patent Application Serial No. PCT/IB2009/005042 filed on Jan. 28, 2009, filed on Jan. 28, 2008, filed on priority. All the contents and disclosures of the aforementioned patent applications are incorporated herein by reference.

Background of the invention

Calcium is generally considered to be a major element of bone health. However, not all calcium is present in the same form, and there are differences in the relative bioavailability of different forms of calcium, which in turn determines the amount of calcium that can enter the systemic circulation. Other important elements are needed to maintain bone health, and tips for mentioning the potential interaction of these elements with each other can be found in the literature. However, the effects of ingestion, calcium utilization, and ultimately bone health have not been systematically studied. In addition, vitamins such as D ₃ and K ₂ have also been thought to be associated with increased calcium intake and bone mineral density (BMD); however, among various bioavailable elements such as calcium, magnesium and zinc, and vitamins The interaction remains unclear. In addition, the complex environment of the gastrointestinal tract plays a leading role in the absorption of elements. In particular, cations and anions can significantly alter the solubility of elemental salts in the gastrointestinal tract (GIT). But the importance of these factors determining the bioavailability of elements has not been thoroughly discussed. In the present invention, a calcium supplement containing an ideal amount of calcium, magnesium, zinc and vitamin D3 acetate is described. In this supplement, the daily dose of calcium is significantly lower than the dose of conventional calcium supplements.

Summary of invention

The present invention provides a dietary supplement comprising an acetate of calcium, magnesium and zinc. The supplement further comprises vitamin D _3. The preparation is highly soluble in water, gastric juice and intestinal fluid. The absorption of the elements is high and the dose required to maintain bone health is about one-quarter to one-third of the traditional calcium dose.

Detailed description of the preferred embodiment

As used herein, fruit juice refers to fruit juices containing fruit juices, fruit juices, natural juices or artificial juices.

The present invention describes an acetate supplement containing calcium, magnesium and zinc. Wherein a solution for the supplement may further contain vitamin D _3.

In one embodiment, the composition of the present invention contains a calcium to magnesium weight ratio of from 0.5:1 to 2:1, and a preferred embodiment is 0.5:1, 1:1 or 2:1. For example, one embodiment of the invention may contain 220 mg of calcium and 440 mg, 220 mg or 110 mg of magnesium. In another embodiment, the composition contains 100 to 300 mg of calcium and 50 to 150 mg of magnesium.

In one version, the compositions of the present invention comprise a zinc to calcium weight ratio of from about 0.05:1 to about 0.1:1. In still further aspects, the zinc to calcium weight ratio is from about 0.05:1 to about 0.20:1.

One of the protocols of the present invention may contain a daily dose of 10 to 40 mg of zinc.

Wherein a solution composition of the present invention may contain from 400 to 1200IU daily dose of vitamin D _3.

One embodiment, the composition may per 100 to 300 g calcium contains more than 400 to 1200 IU vitamin D _3.

One embodiment of the present invention may contain at least 1200 to 3000IU daily dose of vitamin D _3.

Alternatively, the composition of the present invention may contain Vitamin D 4000IU of ₃ daily dosage.

In a further embodiment, the composition of the present invention may contain Vitamin D 5000IU of ₃ daily dosage.

In another embodiment, the composition of the present invention may contain Vitamin D 6000IU of ₃ daily dosage.

In another embodiment, the composition of the present invention may contain Vitamin D 6000IU of ₃ daily dosage.

In one aspect, the present invention provides a composition comprising calcium or synthetic calcium in the form of an acetate, wherein the composition is further enhanced by binding to magnesium, zinc and vitamins. In one embodiment, the composition is an extract of pearls, corals, oysters or natural minerals prior to reinforcement.

In one embodiment, the composition of the present invention contains magnesium in the form of an acetate. In another embodiment, the composition contains zinc in the form of an acetate.

One of the options, magnesium is obtained by synthesis.

Alternatively, magnesium is an extract of other compounds such as magnesium oxide.

In one embodiment, the composition is more soluble than calcium carbonate at a pH of 7.

In one version, the composition contains more bioavailable calcium per unit weight than calcium carbonate. For example, the composition may contain at least 11% by weight calcium in the form of calcium acetate, at least 5% by weight of magnesium in the form of magnesium acetate, and at least 0.5% by weight zinc present in the form of zinc acetate. In another embodiment, the composition may contain at least 7% by weight of calcium in the form of calcium acetate, at least 7% by weight of magnesium in the form of magnesium acetate, and at least 0.3% by weight of zinc in the form of zinc acetate. . In one embodiment and after, the composition may further contain at least 400IU the form vitamin D _3.

In one aspect, the present invention provides a fruit juice composition comprising the composition described above. In one aspect, the juice can be orange juice, grape juice or radish juice.

The present invention also provides a process for preparing a calcium acetate, magnesium acetate, zinc acetate, and vitamin D tablets _3, comprising the steps of: (i) the calcium composition comprising calcium acetate, magnesium acetate and zinc acetate with vitamin D Mixing the composition of ₃ ; and (ii) mixing the composition obtained in the step (i) with a calcium composition containing calcium acetate, magnesium acetate, and zinc acetate to obtain calcium acetate, magnesium acetate, zinc acetate, and vitamin D. ₃ tablets of calcium composition. In this embodiment, the calcium composition contains at least 14% by weight calcium acetate, at least 7% by weight magnesium acetate, and at least 0.7% by weight zinc acetate.

The invention also provides a tablet prepared by the method described above.

The present invention can be better understood by the following detailed description of the invention. However, those skilled in the art can understand that these specific examples are only for the purpose of illustrating certain specific aspects and certain embodiments of the invention, and The invention is defined by the scope of the following claims.

Throughout this application, several documents or publications are cited. These documents or publications are hereby incorporated by reference in their entirety in their entireties in the entireties in the the the the the the the the As used herein, a transitional term such as "containing" is synonymous with "including", "comprising" or "characterized" and is broad or exaggerable and does not exclude additional, unquoted elements or Method steps.

Example 1 Formulation of Pearl Extract

The pearl extract was prepared using the patented method described in the Research Report of Li and Li (1995). In short, the pearls are first ground to 80-120 mesh. The powder is then soaked in a metered amount of acetic acid and sodium chloride solution. Power is applied to the mixture and lasts for several days. After dilution by water and magnetization, the mixture was filtered and precipitated. The calcium acetate-rich precipitate is air dried for use as a dietary supplement. The contents of the various elements in the extract are given in Table 1:

After the fortification of the magnesium acetate in the extract A1, the ratio of calcium to magnesium is 0.5/1 (A6), 1/1 (A4), and 2/1 (A5). The main elemental components of the pearl extract and the nutritionally fortified mixture are listed in Table 2:

In addition to pearls, the methods described in this example can also be used to extract calcium, magnesium and zinc acetates from natural resources such as corals, oysters and ores. The ingredients of Formulations A1, A4, A5 and A6 can also be achieved by mixing a certain amount of calcium, magnesium and zinc acetate.

Example 2 Nutritional Strengthening of Fruit Juice

Juices contain several types of acids, such as malic acid, citric acid, and the like. These acids can alter the solubility of the three key elements in the formulation, thereby altering the absorption capacity of the three elements when taken in the form of a juice.

The purpose of this study was to evaluate the effect of temperature and storage time on the amount of calcium, magnesium and zinc dissolved in composition A5 after mixing with filtered and unfiltered orange juice, grape juice and radish juice.

Accurately weigh 2.6 grams or 500 mg of composition A5 and add it to 330 mL of water or filtered or unfiltered orange, grape or radish juice. The sample was prepared at 4 degrees Celsius or 21 degrees Celsius and the content of the element was measured by ICP-OES.

Small amounts of calcium, magnesium and zinc were found in orange juice, grape juice and radish juice (Tables 3, 6 and 9). When 2.6 grams of composition A5 was used for the study, temperature and filtration had no effect on the amount of calcium, magnesium and zinc dissolved in composition A5 (Tables 4, 7 and 10).

Similarly, in distilled water, the temperature also had no effect on the amount of elemental dissolution in composition A5 (Table 8).

2.6 g of the composition A5 was added to 300 mL of filtered and unfiltered orange juice and grape juice. The sample stored at 4 ° C for 1 week did not change the amount of calcium, magnesium and zinc dissolved in the sample (Table 4 and 7). However, when 500 mg of the composition A5 was used, the dissolved amounts of calcium and magnesium in the unfiltered orange juice were remarkably lowered (Table 5). The lower calcium and magnesium dissolution in unfiltered orange juice reveals that the pulp in the orange juice may block calcium and magnesium in composition A5. This problem did not occur with radish juice (Table 10).

This set of studies demonstrates that Composition A5 can be used to nutritionally fortify several types of juices and water. 2.6 grams of composition A5 provided three daily doses required to prevent osteoporosis: 300 milligrams of calcium, 150 milligrams of magnesium, and 5.6 milligrams of zinc. 500 mg of the A5 composition can also be used to provide these elements in the form of food.

Example 3 composition of the tablet formula

Since the calcium content in the composition A5 is relatively low, it is necessary to prepare it into a dosage form which is convenient to take. The following formulations were prepared in the form of tablets:

In the above table, the calcium acetate mixture contained 14% calcium acetate, 7% magnesium acetate, and 0.7% zinc acetate. Magnesium stearate is used as a lubricant.

The dried vitamin D ₃ 100 GFP/HP composition (as described in the analytical certificate provided by BASF) is as follows:

Test value: 100,000 IU vitamin D ₃ /g (= 2500 mg vitamin D ₃ /g)

The target weight per vitamin tablet D ₃ is 2.5 mg. Extra 30% excess of a form vitamin D ₃ is added to each and tablets. The manufacturer's assay value is 100000 IU/g, for example 100 IU/mg. Since the tablets are in use each and 2.5 mg (with a 30% excess, such as, compared to 3.25 mg), and therefore each capsule tablet containing at least 250 IU of vitamin D _3.

The tablet is prepared according to the following steps:

Step 1: The resulting calcium acetate mixture was sieved through a 40 mesh and 100/120 mesh screen. The portion that passed the 40 mesh screen but failed to pass the 100/120 mesh screen was used to prepare the formulation. A portion of calcium acetate greater than 40 mesh and less than 100 mesh was not used to prepare the formulation. This fraction was chosen to be similar in size to the other components - vitamin D ₃ and Kollidon Va 64.

Step 2: Mixture 01: 6.5 g of mixed dry vitamin D ₃ 100 GFP/HP and 65 g of Kollidon VA 64 were mixed using a small tumble mixer at 25 rpm for 5 minutes to give a mixture 01.

Step 3: Mixture 02: Mix 250 g of the mixed calcium acetate mixture prepared in Step 01 (3.49 times the weight of the mixture 01) with the mixture 01 prepared in Step 2 for 5 minutes to obtain a mixture 02 (using a small tumble mixer and 25-30 rpm).

Step 4: Mixture 03: 250 g of the mixed calcium acetate mixture prepared in Step 1 was mixed with the mixture 02 prepared in Step 3 for 5 minutes to give a mixture 03 (using a double cone mixer and a rotation speed of 25-30 rpm).

Step 5: Mixture 04: 600 g of the mixed calcium acetate mixture prepared in Step 1 was mixed with the mixture 03 prepared in Step 4 for 9 minutes to give a mixture of 04 (using a double cone mixer and a rotation speed of 25-30 rpm).

Step 6: Mixture 05: 5.86 g of the mixed magnesium stearate was mixed with the mixture 04 prepared in Step 5 for 2 minutes.

Step 7: The final mixture prepared in the above step was mixed with a target tablet having a weight of 588.7 g using a tabletop rotator.

The following formulations are also prepared in the form of tablets:

In the above table, the calcium acetate mixture contained 14% calcium acetate, 7% magnesium acetate, and 0.7% zinc acetate. Magnesium stearate is used as a lubricant.

The dried vitamin D ₃ 100 GFP/HP composition (as described by the analytical certificate provided by BASF) is as described in Table 12.

Test value: 100,000 IU of vitamin D ₃ /g (= 2500 mg of vitamin D ₃ /g) The target weight of each vitamin tablet D ₃ is 5 mg. An additional 30% was added to each and form vitamin D ₃ in the tablet as a decomposition loss. The manufacturer's assay value is 100000 IU/g, for example 100 IU/mg. Since each piece 5mg tablets are used (such as with an excess of 30%, compared to 6.5mg), therefore each capsule tablet containing at least 500 IU of vitamin D _3.

The tablets were prepared according to the following procedure: Step 1: The resulting calcium acetate mixture was sieved through a 40 mesh and 100/120 mesh screen. The portion that passed the 40 mesh screen but failed to pass the 100/120 mesh screen was used to prepare the formulation. A portion of calcium acetate greater than 40 mesh and less than 100 mesh was not used to prepare the formulation. This fraction was chosen to be similar in size to the other components - vitamin D ₃ and Kollidon Va 64.

Step 2: Mixture 01: 13 g of the mixed dry vitamin D ₃ 100 GFP/HP and 130 g of Kollidon VA 64 were mixed using a small tumble mixer at 25 rpm for 5 minutes to give a mixture 01.

Step 3: Mixture 02: Mix 500 g of the mixed calcium acetate mixture (mixture 01 * 3.49) prepared in step 01 with the mixture 01 prepared in step 2 for 5 minutes to obtain a mixture 02 (using a small tumble mixer and 25- 30 rpm).

Step 4: Mixture 03: 500 g of the mixed calcium acetate mixture prepared in Step 1 was mixed with the mixture 02 prepared in Step 3 for 5 minutes to obtain a mixture 03 (using a double cone mixer and a rotation speed of 25-30 rpm).

Step 5: Mixture 04: The 1200 g of the mixed calcium acetate mixture prepared in Step 1 was mixed with the mixture 03 prepared in Step 4 for 9 minutes to give a mixture of 04 (using a double cone mixer and a rotation speed of 25-30 rpm).

Step 6: Mixture 05: 11.72 g of the mixed magnesium stearate was mixed with the mixture 04 prepared in Step 5 for 2 minutes.

Step 7: The final mixture prepared in the above step was mixed with a target tablet weighing 1.17 g using a tabletop rotator.

The specifications of these two formulations have been proven to be acceptable to the test population.

Claims (11)

A method tablet calcium acetate, magnesium acetate, zinc acetate, and form vitamin D ₃ is prepared containing, comprising the steps of: (i) containing calcium acetate, magnesium acetate and zinc acetate, calcium composition is mixed with a composition comprising form vitamin D ₃ in And (ii) mixing the composition obtained in step (i) with a calcium composition comprising calcium acetate, magnesium acetate and zinc acetate; and (iii) performing one or more mixing steps, in each of said steps calcium composition from a combination of the first step of mixing the product obtained with another containing calcium acetate, magnesium acetate, zinc acetate, and mixing; to obtain a composition containing calcium acetate, magnesium acetate, zinc acetate, and the form vitamin D _3, and this tableting composition thus prepared contained calcium acetate, magnesium acetate, zinc acetate and vitamin D tablets _3, wherein said tablet contains at least 4% of calcium, at least 5% magnesium, zinc and at least 0.2%, the tablet Contains a calcium to magnesium weight ratio of 0.5:1 to 2:1. The method of claim 1, wherein the calcium composition comprises at least 14% by weight calcium acetate, at least 7% magnesium acetate, and at least 0.7% zinc acetate. A tablet prepared by the method of claim 1 of the patent application. For example, the tablet of claim 3, wherein the tablet contains a weight ratio of zinc to calcium of 0.05:1 to 0.20:1. A tablet according to claim 3, wherein the tablet contains a daily dose of 5 to 40 mg of zinc. The scope of patent tablet Item 3, wherein the tablet contains 400 to 3000IU daily dose of vitamin D _3. A tablet according to claim 3, wherein the tablet contains a daily dose of 50 to 500 mg of calcium and 25 to 500 mg of magnesium. A tablet according to claim 3, wherein the tablet contains a daily dose of 100 to 300 mg of calcium and 50 to 150 mg of magnesium. A tablet according to claim 3, wherein the tablet contains 100 to 300 mg of calcium, and contains 400 to 1200 IU of vitamin D ₃ . For example, the tablet of claim 3, wherein the tablet contains 220 mg of calcium, and contains 400 to 1200 IU of vitamin D ₃ . A tablet according to claim 3, for use in the preparation of a fortified juice composition.