US3898325A - Method and preparations for relieving pain and producing analgesia - Google Patents

Method and preparations for relieving pain and producing analgesia Download PDF

Info

Publication number
US3898325A
US3898325A US398601A US39860173A US3898325A US 3898325 A US3898325 A US 3898325A US 398601 A US398601 A US 398601A US 39860173 A US39860173 A US 39860173A US 3898325 A US3898325 A US 3898325A
Authority
US
United States
Prior art keywords
histamine
hyaluronidase
pain
solution
units
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US398601A
Inventor
Emanuel Revici
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
PAYN BENJAMIN R
American Lipids Corp
Original Assignee
American Lipids Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by American Lipids Corp filed Critical American Lipids Corp
Priority to US398601A priority Critical patent/US3898325A/en
Priority to CA209,488A priority patent/CA1023265A/en
Priority to DE19742444652 priority patent/DE2444652A1/en
Priority to NL7412346A priority patent/NL7412346A/en
Priority to GB4084774A priority patent/GB1460325A/en
Priority to FR7431674A priority patent/FR2243694B1/fr
Application granted granted Critical
Publication of US3898325A publication Critical patent/US3898325A/en
Assigned to BIOREX CORP. reassignment BIOREX CORP. ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: BIOREX LTD.
Assigned to PAYN, BENJAMIN R. reassignment PAYN, BENJAMIN R. ASSIGNMENT OF ASSIGNORS INTEREST. Assignors: BIOREX CORP. A CORP OF DE
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46Hydrolases (3)
    • A61K38/47Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases

Definitions

  • ABSTRACT A method of treating a host for inducing relief of pain or anesthesia which comprises administering histamine, its salts, or an agent inducing histamine release, and a dispersing agent such as hyaluronidase, at the place of the painful area or at the place indicated for acupuncture for the painful site.
  • This invention relates to a method and preparations for relieving pain and producing analgesia.
  • histamine is used herein in its generic sense, to include histamine, its non-toxic salts, compounds which induce histamine release in the body and histamine derivatives which produce a similar pharmacological activity within the body.
  • Histamine its non-toxic salts, compounds inducing histamine release, and histamine derivatives having a similar pharmacological activity in the body are well known and their properties and pharmacological action well documented in the literature. All such compounds are operable so long as they are capable of depositing directly or indirectly a sufficient amount of histamine in combination with hyaluronidase to induce analgesia or relief of pain.
  • the main object is to impart by injection to the painful area or at the acupuncture sites histamine or a related compound having the same pharmacological action as histamine in combination with hyaluronidase. Whether this is accomplished by use of histamine itself or its non-toxic salts, or in any other manner, is not material and is to be considered within the present invention.
  • the dispersing or spreading factor can be a hyaluronidase of different origins, for example, from honey-bee venom, snake venom, etc. z-N-acetylglucosamidase has been found to be most efficient. These dispersing agents or factors and the methods by which they may be obtained are well known in the art.
  • the pain relieving or analgesic compositions of this invention can be prepared for injection by placing the histamine compound and hyaluronidase in a suitable medium, such as water, saline solution, isotonic solution, etc., with proper sterilization, as will be apparent to those skilled in the art.
  • a suitable medium such as water, saline solution, isotonic solution, etc.
  • the histamine compound and the hyaluronidase can be separately injected into the painful area or the acupuncture site for that painful area, but it is, of course, more convenient to combine the histamine compound and the hyaluronidase in a convenient solution.
  • the concentration of the hyaluronidase enzyme because of its variable activity, depending upon its source and other well known factors, is given in units as set by the National Formulary.
  • the unit concentration is given on each package as units NF (TR) per volume of weight.
  • histamine and/0r hyaluronidase that can be injected will depend upon the particular patient being treated, the extent of the painful area, and the degree of pain. A sufficient amount of the histamine compound and the hyaluronidase should, of course, be injected to overcome the pain as will be apparent to any physician.
  • the minimum amount has so far been determined to be about 0.01 mg., and with respect to the hyaluronidase about 10 units NF (TR), [hereinafter referred to as units or units per ml.]. Lower amounts could be used if conditions so indicate.
  • the maximum amount of the histamine compound that can be used willdepend somewhat upon the patient and his tolerance to flushes due to histamine reaction. Generally, amounts up to 0.5 mg. can be tolerated.
  • hyaluronidase The maximum amount of hyaluronidase that can be used will again depend upon the particular patient to be treated as well as the amount of histamine being injected. Investigation to date indicated that one would not require more than 50 units of hyalurondase.
  • the preparations of this invention can be prepared in such a manner so that the patient can receive between about 0.01 mg. and 0.05 mg. of histamine and between about 10 and about 50 units of hyaluronidase.
  • Experiments to date have shown that an injection of 0.02 mg. of histamine and 10 units of hyaluronidase is advantageous.
  • the solutions can he made up in varying concentrations and the total volume injected will, of course, depend upon the concentration of the solution. For example, if a solution is made up to contain 0.02 mg. of histamine per ml. and 10 units of hyaluronidase per ml., an injection of 1 ml. of this solution into the painful area or the acupuncture site should be sufficient.
  • the solutions can be injected into the painful area by anymeans sufficient to relieve the pain. such as, subcataneously, or deeper into the tissues, periaticular, or even in the articulations, or in the sites used for acupuncture.
  • the composition or preparation may be injected into a plurality of places in the painful area, such asin Example l,set forth below.
  • Such a procedure is referred to herein as infiltration of the painful area. For example, in bursitis, at times, no burt can be located and in which case the entire painful area, the shoulder for example.
  • the two main defects of the method are controlled by this infiltration technique. using more diluted solutions of histamine.
  • the method of this invention can also be practiced by injecting the preparations at the acupuncture sites for the areas in which it is desired to relieve pain or produce analgesia.
  • These sites are well known and are described for example, in ACU- PUNCTURE THERAPY, CURRENT CHINESE PRACTICE, by T. Tan, Y-C. Tan and Veith, Temple University Press, Philadelphia, 1973.
  • One advantage of this acupuncture technique is the fact that the results are not the function of the capacity of the individual to respond to the needle insertion with the liberation of histamine, and the use of this invention results in increased responses in the patient.
  • Another advantage is the fact that the injection of the preparations, according to this invention, will affect the entire area or acupuncture site rather than just a single point, and the chances of having the necessary acupuncture site influenced is thus highly increased.
  • the preparations of thisinvention can thus be used for the treatment of different conditions for which acupuncture is presently used, such as for the induction of anesthesia for surgical interventions.
  • EXAMPLE 1 A 60 year old male with severe pain and totally immobilized by a frozen shoulder" due to bursitis. The condition had gotten progressively worse over the last two months and did not respond to various treatments. From a solution containing 0.2 mg. of histamine phosphate and l0 units of hyaluronidase per ml., 2' ml. divided in 4 injections were injected in the painful spots. The pain disappeared in less than 6 minutes, with recovery of movement. Seen after 2 weeks, the; good effects were persistent.
  • EXAMPLE 3 A 50 year old male with pain due to a sciatica of the left. leg, not responding to treatments for the last month. A total of 3 ml. of a preparation containing 0.05 mg. of histamine and 10 units of hyaluronidase per ml. was injecteddeep subcutaneously in 5 different painful spots. The pain disappeared and remained as such after 2 months.
  • EXAMPLE 4 A year old female .with pains in the left knee, and unable to localize the pain otherwise than the entire anterior area of the knee. A subcutaneous infiltration of this region with 10 ml. of a solution containing 0.01 mg. per ml. of histamine phosphate and 10 units of hyaluronidase per ml. was followed by the disappearance and without recurrence of the pain after 12 days..
  • EXAMPLE 6 A 62 year old female with severe pain in the left sacroiliac articulation, persisting for months. A subcataneous injection of 0.5 ml. of a solution containing 0.2 mg. per ml. of histamine and 10 units of hyaluronidase per ml. at the painful area did not completely suppress the pain after l5 minutes. A same amount of the solution injected deep into the articulation fully controlled the pain, with the effect still persisting after 3 weeks.
  • EXAMPLE 7 A 50 year old male with acancer of the spine, at the 10-12 D and 1 D forwhich a decompressioin intervention was performed. The patient had very severe pain, on both sides of the lesion, only insufficiently controlled by opiates. From a solution containing 0.2 mg. of histamine phosphate per ml. and 10 units of hyaluronidase per ml., several injections totalling 1.5. ml. weremade only at the right side of the spine. The pain disappeared after 6 minutes and still did not reappear after one week, while the pain persisted unchanged in the left side of the spine. The same injection in left side hadfthe same good effect.
  • EXAMPLE 8 A 40 year old male with severe backache. The pain- I ful area was injected with 2 ml. of a 0.1 percent by weight solution of compound 48/80 and l units of hyaluronidase per ml. in a saline (sterilized by filtration). The pain was controlled in about 15 minutes and the effect still persisted after one week.
  • EXAMPLE 9 A 63 year old male with pains in the elbow after playing tennis. The pain persisted for weeks, in spite of treatment. A local infiltration of 7.5 ml. of a solution containing 0.02 mg. per ml. of histamine and 20 units of hyaluronidase per ml. was injected locally. The pain disappeared in minutes. The patient did not have any flushing sensation.
  • EXAMPLE 10 A 30 year old male with a very painful shoulder of osteoarthritic nature. An infiltration of the entire painful area. with ml. ofa solution containing 0.1 mg. of histamine per ml. and 10 units of hyaluronidase was made. The pain was controlled in less than 10 minutes. The patient remained without pain 6 weeks after the infiltration. The patient, who had a severe histaminic reaction because of a prior use of histamine for a gastric test. with headache. itching and vision troubles did not have any adverse reaction after treatment.
  • abdominal pain from ovary inflammation and gallbladder colics wee controlled by deep subcutaneous injections in the painful areas. Even cancer pains responded well to the injections. Good results were obtained for different neuralgias. such as sciatica. tic douloureux. post Zonz Zoster neuralgia. with injections made locus dolendi" (painful spots). The effects were good also in fractures and especially in residual pains after trauma. ln gen eral. with only very few exemptions. the results in more than 100 cases treated are exceptionally good. with not only the pain immediately controlled and with functional recovery, but with the results lasting for a long period of time, weeks or even months after the injections. The pain entirely disappears in less than about 15 minutes in most cases. In some cases the pain was felt after one or two days, but in these cases the pain was felt in areas other than those injected. No local numbness was noted.
  • a method of relieving pain or producing analgesia in a host which comprises injecting a solution of histamine. or its non-toxic salts. and a hyaluronidase at the painful area or at the acupuncture sites for the area in which it is desired to relieve pain or produce analgesia in a host in a sufficient amount to relieve'the pain or produce analgesia.
  • hyaluronidase is z-N-Acetylglucosamidase hyaluronidase.
  • Preparations for use in relieving pain or for producing analgesia which comprise a sterile solution of histamine or its non-toxic salts, and a hyaluronidase containing between about .01 mg. to about 0.5 mg. histamine per ml. and between about 10 to about 50 NF (TR) units of the hyaluronidase.

Abstract

A method of treating a host for inducing relief of pain or anesthesia which comprises administering histamine, its salts, or an agent inducing histamine release, and a dispersing agent such as hyaluronidase, at the place of the painful area or at the place indicated for acupuncture for the painful site.

Description

United States Patent 1 1 Revici Aug. 5, 1975 [75] Inventor: Emanuel Revici, New York, NY.
[73] Assignee: American Lipids Corporation, New
York. NY.
[22] Filed: Sept. 19, 1973 [21] App]. No.: 398,601
[52] US. Cl 424/94; 424/273 [51] Int. Cl. A61K 19/00 [58] Field of Search 424/94, 273
[56] References Cited OTHER PUBLICATIONS Merck Index, 7th Edition (I960) pages 520 & 521.
Societe, Chem. Abst. Vol. 75 (1971) page 52828u.
Lechat. Chem. Abst. Vol. 71 (1969) page 69229qv Keele, Chem. Abst. Vol. 67 (1967) page 1507r.
Barnard. Chem. Abst. Vol. 60 (1964), page 5287a.
Primary E.\'aminer-Sam Rosen Attorney, Agent, or FirmPennie & Edmonds l 5 7 1 ABSTRACT A method of treating a host for inducing relief of pain or anesthesia which comprises administering histamine, its salts, or an agent inducing histamine release, and a dispersing agent such as hyaluronidase, at the place of the painful area or at the place indicated for acupuncture for the painful site.
9 Claims, N0 Drawings METHOD AND PREPARATIONS FOR RELIEVING PAIN AND PRODUCING ANALGESIA BACKGROUND OF THE INVENTION 1. Field of the Invention:
This invention relates to a method and preparations for relieving pain and producing analgesia.
2. Description of the Prior Art:
A great deal of research has been performed on the effect of histamine and related compounds, both in vivo and in vitro. The literature on this subject is so vast and conflicting that it is simply not practical to set forth any meaningful discussion on the subject. For example, Rosenthal et al. have reported in Am. J. Physiol. 155, 18690 1948) that painful sensations are produced by the injection of histamine and in the Proc. Soc. Ecptl. Biol. Med. 74, 167-70 (1950) that histamine introduced into the superficial layers of human skin causes an immediate well as latent painful sensation. Jacob et al.. Am. inst. Pasteur 81, 12892 (1951), have reported that histamine dil-ICI given to rats subcutaneously or intraperitoneally for 6 to 30 days decreased their sensitivity to thermal induced pain, but which returned after cessation of treatment.
Similarly a great deal of research has been performed with spreading agents such as the hyaluronidase enzyme. Hyaluronidase has been used alone and in combination with various drugs. The use of hyaluronidase and histamine has also been studied. For example, it has been reported by Seelich et al., Nature 168, 1125 (1951 that histamine does not neutralize heparin inhibitian of hyaluronidase and by Mathies et al., in Z. ges. exptel. Med. 133, 3237 (1960), that the inhibitary action of phenylbutazone against hyaluronidase could be blocked by the simultaneous administration of an antihistaminic agent. A vast amount of additional publications exist, both with respect to histamine and hyaluronidase, none of which, to applicants knowledge, disclose or teach the invention disclosed and claimed herein.
SUMMARY OF THE INVENTION It has been found that administering histamine, its salts. compounds inducing histamine release, and dispersing agent such as hyaluronidase, or derivatives of histamine, having substantially the same pharmacological activity of histamine, directly to the painful area or at the sites indicated for acupuncture for that painful area, will relieve the pain and produce analgesia at the painful area.
The term. histamine. is used herein in its generic sense, to include histamine, its non-toxic salts, compounds which induce histamine release in the body and histamine derivatives which produce a similar pharmacological activity within the body.
DESCRIPTION OF THE PREFERRED EMBODIMENTS Histamine. its non-toxic salts, compounds inducing histamine release, and histamine derivatives having a similar pharmacological activity in the body are well known and their properties and pharmacological action well documented in the literature. All such compounds are operable so long as they are capable of depositing directly or indirectly a sufficient amount of histamine in combination with hyaluronidase to induce analgesia or relief of pain. The main object is to impart by injection to the painful area or at the acupuncture sites histamine or a related compound having the same pharmacological action as histamine in combination with hyaluronidase. Whether this is accomplished by use of histamine itself or its non-toxic salts, or in any other manner, is not material and is to be considered within the present invention.
The dispersing or spreading factor can be a hyaluronidase of different origins, for example, from honey-bee venom, snake venom, etc. z-N-acetylglucosamidase has been found to be most efficient. These dispersing agents or factors and the methods by which they may be obtained are well known in the art.
The pain relieving or analgesic compositions of this invention can be prepared for injection by placing the histamine compound and hyaluronidase in a suitable medium, such as water, saline solution, isotonic solution, etc., with proper sterilization, as will be apparent to those skilled in the art.
The histamine compound and the hyaluronidase can be separately injected into the painful area or the acupuncture site for that painful area, but it is, of course, more convenient to combine the histamine compound and the hyaluronidase in a convenient solution.
The concentration of the hyaluronidase enzyme, because of its variable activity, depending upon its source and other well known factors, is given in units as set by the National Formulary. The unit concentration is given on each package as units NF (TR) per volume of weight.
The amount of histamine and/0r hyaluronidase that can be injected will depend upon the particular patient being treated, the extent of the painful area, and the degree of pain. A sufficient amount of the histamine compound and the hyaluronidase should, of course, be injected to overcome the pain as will be apparent to any physician.
With respect to the histamine compound, the minimum amount has so far been determined to be about 0.01 mg., and with respect to the hyaluronidase about 10 units NF (TR), [hereinafter referred to as units or units per ml.]. Lower amounts could be used if conditions so indicate.
The maximum amount of the histamine compound that can be used willdepend somewhat upon the patient and his tolerance to flushes due to histamine reaction. Generally, amounts up to 0.5 mg. can be tolerated.
The maximum amount of hyaluronidase that can be used will again depend upon the particular patient to be treated as well as the amount of histamine being injected. Investigation to date indicated that one would not require more than 50 units of hyalurondase.
Thus, the preparations of this invention can be prepared in such a manner so that the patient can receive between about 0.01 mg. and 0.05 mg. of histamine and between about 10 and about 50 units of hyaluronidase. Experiments to date have shown that an injection of 0.02 mg. of histamine and 10 units of hyaluronidase is advantageous.
The solutions can he made up in varying concentrations and the total volume injected will, of course, depend upon the concentration of the solution. For example, if a solution is made up to contain 0.02 mg. of histamine per ml. and 10 units of hyaluronidase per ml., an injection of 1 ml. of this solution into the painful area or the acupuncture site should be sufficient.
The solutions can be injected into the painful area by anymeans sufficient to relieve the pain. such as, subcataneously, or deeper into the tissues, periaticular, or even in the articulations, or in the sites used for acupuncture. Depending upon the area of pain, one injection may suffice or,- if the painful area is larger, the composition or preparation may be injected into a plurality of places in the painful area, such asin Example l,set forth below. Such a procedure is referred to herein as infiltration of the painful area. For example, in bursitis, at times, no burt can be located and in which case the entire painful area, the shoulder for example. may be infiltrated, injecting the total amount of desired histamine and hyaluronidase into the shoulder at a plurality of sites. In this case it may be, at times, desirable to have a more diluted solution, so that a larger area can be infiltrated and, at the same time, decrease the chance of-any histamine reaction by the patient. Thus, the two main defects of the method, the missing-of the painful spots and the flushes due to histaminic action, are controlled by this infiltration technique. using more diluted solutions of histamine.
As previously mentioned the method of this invention can also be practiced by injecting the preparations at the acupuncture sites for the areas in which it is desired to relieve pain or produce analgesia. These sites are well known and are described for example, in ACU- PUNCTURE THERAPY, CURRENT CHINESE PRACTICE, by T. Tan, Y-C. Tan and Veith, Temple University Press, Philadelphia, 1973.
One advantage of this acupuncture technique is the fact that the results are not the function of the capacity of the individual to respond to the needle insertion with the liberation of histamine, and the use of this invention results in increased responses in the patient. Another advantage is the fact that the injection of the preparations, according to this invention, will affect the entire area or acupuncture site rather than just a single point, and the chances of having the necessary acupuncture site influenced is thus highly increased. The preparations of thisinvention can thus be used for the treatment of different conditions for which acupuncture is presently used, such as for the induction of anesthesia for surgical interventions.
It has also been noted that together with the suppression of the pain, the evolution of lesions also appears to be influenced.
In all cases where a patient is treated, as a precautionary measure, an anthistamine injection or adrenaline for injection was kept available in case of hypersensitivity to histamine. It is interesting to note, however, that in over 100 cases treated so far there was no need to use either the histaminic preparation or adrenaline, even in a case (Example l) of the patient who had a history of servere histamininc reactions.
The following examples illustrate the practise of the invention:
EXAMPLE 1 A 60 year old male with severe pain and totally immobilized by a frozen shoulder" due to bursitis. The condition had gotten progressively worse over the last two months and did not respond to various treatments. From a solution containing 0.2 mg. of histamine phosphate and l0 units of hyaluronidase per ml., 2' ml. divided in 4 injections were injected in the painful spots. The pain disappeared in less than 6 minutes, with recovery of movement. Seen after 2 weeks, the; good effects were persistent.
EXAMPLE ,2
A 58 year old female with severe arthritis pain in the coccidial region for several months. The pain could not be controlled by various treatments. From a solution containing 0.05 mg. of histamine phosphate and 10 units of. hyaluronidase per ml. 1 ml. was injected in the painfularea. The pain disappeared in 4 minutes and remained as such at an examination one month later.
EXAMPLE 3 A 50 year old male with pain due to a sciatica of the left. leg, not responding to treatments for the last month. A total of 3 ml. of a preparation containing 0.05 mg. of histamine and 10 units of hyaluronidase per ml. was injecteddeep subcutaneously in 5 different painful spots. The pain disappeared and remained as such after 2 months.
EXAMPLE 4 EXAMPLE 5 A year old female .with pains in the left knee, and unable to localize the pain otherwise than the entire anterior area of the knee. A subcutaneous infiltration of this region with 10 ml. of a solution containing 0.01 mg. per ml. of histamine phosphate and 10 units of hyaluronidase per ml. was followed by the disappearance and without recurrence of the pain after 12 days..
EXAMPLE 6 A 62 year old female with severe pain in the left sacroiliac articulation, persisting for months. A subcataneous injection of 0.5 ml. of a solution containing 0.2 mg. per ml. of histamine and 10 units of hyaluronidase per ml. at the painful area did not completely suppress the pain after l5 minutes. A same amount of the solution injected deep into the articulation fully controlled the pain, with the effect still persisting after 3 weeks.
EXAMPLE 7 A 50 year old male with acancer of the spine, at the 10-12 D and 1 D forwhich a decompressioin intervention was performed. The patient had very severe pain, on both sides of the lesion, only insufficiently controlled by opiates. From a solution containing 0.2 mg. of histamine phosphate per ml. and 10 units of hyaluronidase per ml., several injections totalling 1.5. ml. weremade only at the right side of the spine. The pain disappeared after 6 minutes and still did not reappear after one week, while the pain persisted unchanged in the left side of the spine. The same injection in left side hadfthe same good effect.
EXAMPLE 8 A 40 year old male with severe backache. The pain- I ful area was injected with 2 ml. of a 0.1 percent by weight solution of compound 48/80 and l units of hyaluronidase per ml. in a saline (sterilized by filtration). The pain was controlled in about 15 minutes and the effect still persisted after one week.
EXAMPLE 9 A 63 year old male with pains in the elbow after playing tennis. The pain persisted for weeks, in spite of treatment. A local infiltration of 7.5 ml. of a solution containing 0.02 mg. per ml. of histamine and 20 units of hyaluronidase per ml. was injected locally. The pain disappeared in minutes. The patient did not have any flushing sensation.
EXAMPLE 10 A 30 year old male with a very painful shoulder of osteoarthritic nature. An infiltration of the entire painful area. with ml. ofa solution containing 0.1 mg. of histamine per ml. and 10 units of hyaluronidase was made. The pain was controlled in less than 10 minutes. The patient remained without pain 6 weeks after the infiltration. The patient, who had a severe histaminic reaction because of a prior use of histamine for a gastric test. with headache. itching and vision troubles did not have any adverse reaction after treatment.
As can be seen from the above examples, abdominal pain from ovary inflammation and gallbladder colics wee controlled by deep subcutaneous injections in the painful areas. Even cancer pains responded well to the injections. Good results were obtained for different neuralgias. such as sciatica. tic douloureux. post Zonz Zoster neuralgia. with injections made locus dolendi" (painful spots). The effects were good also in fractures and especially in residual pains after trauma. ln gen eral. with only very few exemptions. the results in more than 100 cases treated are exceptionally good. with not only the pain immediately controlled and with functional recovery, but with the results lasting for a long period of time, weeks or even months after the injections. The pain entirely disappears in less than about 15 minutes in most cases. In some cases the pain was felt after one or two days, but in these cases the pain was felt in areas other than those injected. No local numbness was noted.
I claim:
1. A method of relieving pain or producing analgesia in a host which comprises injecting a solution of histamine. or its non-toxic salts. and a hyaluronidase at the painful area or at the acupuncture sites for the area in which it is desired to relieve pain or produce analgesia in a host in a sufficient amount to relieve'the pain or produce analgesia.
2. The method of claim 1, wherein the preparation is infiltrated at the painful area.
3. The method of claim 1 in which the histamine and hyaluronidase are injected in admixture.
4. A method of claim 1, wherein the hyaluronidase is z-N-Acetylglucosamidase hyaluronidase.
5. The method of claim 1, wherein the solution contains from about .01 to about 0.5 mgs. of histamine per ml.
6. The method of claim 5, wherein the solution contains from about 10 to about 50 NF (TR) units of hyaluronidase.
7. Preparations for use in relieving pain or for producing analgesia which comprise a sterile solution of histamine or its non-toxic salts, and a hyaluronidase containing between about .01 mg. to about 0.5 mg. histamine per ml. and between about 10 to about 50 NF (TR) units of the hyaluronidase.
8. The preparation of claim 7 wherein the ingredients are combined with a non-toxic liquid carrier.
9. A preparation of claim 8, wherein the carrier is water, saline solution or an isotonic solution.

Claims (9)

1. A METHOD OF RELIEVING PAIN OR PRODUCING ANALGESIA IN A HOST WHICH COMPRISES INJECTING A SOLUTION OF HISTAMINE, OR ITS NON-TOXIC SALTS, AND A HYALURONIDASE AT THE PAINFUL AREA OR AT THE ACUPUNCTURE SITES FOR THE AREA IN WHICH IT IS DESIRED TO RELIEVE PAIN OR PRODUCE ANALGESIA IN A HOST IN A SUFFICIENT AMOUNT TO RELIEVE THE PAIN OR PRODUCE ANALGESIA.
2. The method of claim 1, wherein the preparation is infiltrated at the painful area.
3. The method of claim 1 in which the histamine and hyaluronidase are injected in admixture.
4. A method of claim 1, wherein the hyaluronidase is z-N-Acetylglucosamidase hyaluronidase.
5. The method of claim 1, wherein the solution contains from about .01 to about 0.5 mgs. of histamine per ml.
6. The method of claim 5, wherein the solution contains from about 10 to about 50 NF (TR) units of hyaluronidase.
7. Preparations for use in relieving pain or for producing analgesia which comprise a sterile solution of histamine or its non-toxic salts, and a hyaluronidase containing between about .01 mg. to about 0.5 mg. histamine per ml. and between about 10 to about 50 NF (TR) units of the hyaluronidase.
8. The preparation of claim 7 wherein the ingredients are combined with a non-toxic liquid carrier.
9. A preparation of claim 8, wherein the carrier is water, saline solution or an isotonic solution.
US398601A 1973-09-19 1973-09-19 Method and preparations for relieving pain and producing analgesia Expired - Lifetime US3898325A (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
US398601A US3898325A (en) 1973-09-19 1973-09-19 Method and preparations for relieving pain and producing analgesia
DE19742444652 DE2444652A1 (en) 1973-09-19 1974-09-18 MEANS FOR CONTROLLING LOCAL PAIN
NL7412346A NL7412346A (en) 1973-09-19 1974-09-18 PROCEDURE FOR PREPARING A PREPARATION WITH ANALGETIC AND ANALGETIC ACTION.
CA209,488A CA1023265A (en) 1973-09-19 1974-09-18 Method and preparation for relieving pain and producing analgesia
GB4084774A GB1460325A (en) 1973-09-19 1974-09-19 Pharmaceutical composition intended for relieving pain and producing analgesia
FR7431674A FR2243694B1 (en) 1973-09-19 1974-09-19

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US398601A US3898325A (en) 1973-09-19 1973-09-19 Method and preparations for relieving pain and producing analgesia

Publications (1)

Publication Number Publication Date
US3898325A true US3898325A (en) 1975-08-05

Family

ID=23576006

Family Applications (1)

Application Number Title Priority Date Filing Date
US398601A Expired - Lifetime US3898325A (en) 1973-09-19 1973-09-19 Method and preparations for relieving pain and producing analgesia

Country Status (6)

Country Link
US (1) US3898325A (en)
CA (1) CA1023265A (en)
DE (1) DE2444652A1 (en)
FR (1) FR2243694B1 (en)
GB (1) GB1460325A (en)
NL (1) NL7412346A (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5102783A (en) * 1990-01-12 1992-04-07 Vetrepharm, Inc. Composition and method for culturing and freezing cells and tissues
WO1995023601A1 (en) * 1994-03-02 1995-09-08 Professional Pharmaceutical, Inc. Method and composition for topical treatment of damaged tissue using histamine phosphate as active ingredient
US20030017145A1 (en) * 1999-01-08 2003-01-23 Kristoffer Hellstrand Treatment and prevention of reactive oxygen metabolite-mediated cellular damage
US20100042137A1 (en) * 2008-02-19 2010-02-18 Oronsky Bryan T Acupuncture and acupressure therapies
CN106714824A (en) * 2014-07-16 2017-05-24 纽约大学 Use of hyaluronidase for treatment of muscle stiffness
US10232048B1 (en) 2014-11-18 2019-03-19 Divine Api-Logics, LLC Apitherapy method and composition

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
Barnard, Chem. Abst. Vol. 60 (1964), page 5287a. *
Keele, Chem. Abst. Vol. 67 (1967) page 1507r. *
Lechat, Chem. Abst. Vol. 71 (1969) page 69229q. *
Merck Index, 7th Edition (1960) pages 520 & 521. *
Societe, Chem. Abst. Vol. 75 (1971) page 52828u. *

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5102783A (en) * 1990-01-12 1992-04-07 Vetrepharm, Inc. Composition and method for culturing and freezing cells and tissues
WO1995023601A1 (en) * 1994-03-02 1995-09-08 Professional Pharmaceutical, Inc. Method and composition for topical treatment of damaged tissue using histamine phosphate as active ingredient
US20030017145A1 (en) * 1999-01-08 2003-01-23 Kristoffer Hellstrand Treatment and prevention of reactive oxygen metabolite-mediated cellular damage
EP1410798A2 (en) * 1999-01-08 2004-04-21 Maxim Pharmaceuticals, Inc. Treatment and prevention of reactive oxygen metabolite-mediated cellular damage
US20040191239A1 (en) * 1999-01-08 2004-09-30 Kristoffer Hellstrand Treatment and prevention of reactive oxygen metabolite-mediated cellular damage
EP1410798A3 (en) * 1999-01-08 2004-10-13 Maxim Pharmaceuticals, Inc. Treatment and prevention of reactive oxygen metabolite-mediated cellular damage
US20100042137A1 (en) * 2008-02-19 2010-02-18 Oronsky Bryan T Acupuncture and acupressure therapies
CN106714824A (en) * 2014-07-16 2017-05-24 纽约大学 Use of hyaluronidase for treatment of muscle stiffness
US20170202930A1 (en) * 2014-07-16 2017-07-20 New York University Use of hyaluronidase for treatment of muscle stiffness
EP3169351A4 (en) * 2014-07-16 2018-04-11 New York University Use of hyaluronidase for treatment of muscle stiffness
US10307467B2 (en) * 2014-07-16 2019-06-04 New York University Use of hyaluronidase for treatment of muscle stiffness
AU2015289619B2 (en) * 2014-07-16 2020-09-17 New York University Use of hyaluronidase for treatment of muscle stiffness
AU2015289619C1 (en) * 2014-07-16 2021-01-07 New York University Use of hyaluronidase for treatment of muscle stiffness
US11654185B2 (en) 2014-07-16 2023-05-23 New York University Use of hyaluronidase for treatment of muscle stiffness
US10232048B1 (en) 2014-11-18 2019-03-19 Divine Api-Logics, LLC Apitherapy method and composition

Also Published As

Publication number Publication date
GB1460325A (en) 1977-01-06
FR2243694A1 (en) 1975-04-11
FR2243694B1 (en) 1978-07-28
NL7412346A (en) 1975-03-21
DE2444652A1 (en) 1975-03-20
CA1023265A (en) 1977-12-27

Similar Documents

Publication Publication Date Title
Bertelli et al. Hyaluronidase as an antidote to extravasation of Vinca alkaloids: clinical results
Schutzer et al. The treatment of reflex sympathetic dystrophy syndrome.
Salmela et al. Transient radicular irritation after spinal anesthesia induced with hyperbaric solutions of cerebrospinal fluid‐diluted lidocaine 50 mg/ml or mepivacaine 40 mg/ml or bupivacaine 5 mg/ml
CN1997373A (en) Phycotoxins and uses thereof
Hench Effect of jaundice on rheumatoid arthritis
KR20090111916A (en) Pharmaceutical preparation for removing local body fat
Britton et al. Clinical uses of hyaluronidase: a current review
CA2594202A1 (en) Use of resiniferatoxin (rtx) for producing an agent for treating joint pains and method for applying said agent
US3898325A (en) Method and preparations for relieving pain and producing analgesia
Stovner et al. Intrathecal phenol for cancer pain
Bohm Transcutaneous electrical nerve stimulation in chronic pain after peripheral nerve injury
KR19990037550A (en) Treatment method and composition for treatment of sexual dysfunction
Hannington-Kiff Does failed natural opioid modulation in regional sympathetic ganglia cause reflex sympathetic dystrophy?
Burt et al. Heterotransplantation of bladder cancer in the hamster cheek pouch: in vivo testing of cancer chemotherapeutic agents
Lewis et al. The use of high-dose lidocaine in wetting solutions for lipoplasty
Dahl The treatment of plastic induration of the penis (Peyronie's disease)
Drewes et al. Injection therapy for treatment of chronic myofascial pain: a double-blind study comparing corticosteroid versus diclofenac injections
Lu et al. Effect of Comprehensive Care Based on Appropriate Chinese Medicine Techniques on Urinary Retention and Bladder Function Recovery after Total Hysterectomy in Patients with Cervical Cancer
RU2147883C1 (en) Method for treating the cases of upper extremity lymphedema
Khanna et al. Mitomycin C extravasation ulcers
FELDMAN et al. Treatment of senile pruritus with androgens and estrogens
Parkes Diseases of the central nervous system. Relief of pain: headache, facial neuralgia, migraine, and phantom limb.
RU2299733C1 (en) Method for treating patients for degenerative dystrophy diseases of locomotor apparatus and post-traumatic commissure processes
Fraser Clinical Aspects of Acetylcholine—I
RU2350366C1 (en) Method of treatment of traumas of joints consequences

Legal Events

Date Code Title Description
AS Assignment

Owner name: BIOREX CORP., 505 PARK AVE, NEW YORK,N.Y. 10022, A

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:BIOREX LTD.;REEL/FRAME:003854/0521

Effective date: 19810512

AS Assignment

Owner name: PAYN, BENJAMIN R. 575 PARK AVENUE NEW YORK NEW YOR

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:BIOREX CORP. A CORP OF DE;REEL/FRAME:004280/0960

Effective date: 19840710

STCF Information on status: patent grant

Free format text: PATENTED FILE - (OLD CASE ADDED FOR FILE TRACKING PURPOSES)